Immune dysregulation in flea allergy dermatitis--a model for the immunopathogenesis of allergic dermatitis

BACKGROUND: Flea allergy dermatitis (FAD) is a common skin disease in dogs and can be induced experimentally. It often coexists with other allergic conditions. So far no studies have investigated the quantitative production of cytokine mRNA in skin biopsies and peripheral blood mononuclear cells (PBMC) in flea allergic dogs. OBJECTIVE: The aim of our study was to improve the understanding of the immunopathogenesis of allergic dermatitis as a response to fleabites. MATERIAL AND METHODS: Allergic and non-allergic dogs were exposed to fleas. Before and after 4 days of flea exposure mRNA was isolated from biopsies and PBMC. Production of chymase, tryptase, IL-4, IL-5, IL-13, TNF-alpha and IFN-gamma mRNA was measured by real-time RT-PCR. The inflammatory infiltrate in the skin was scored semi-quantitatively. The number of eosinophils, mast cells (MC) and IgE+ cells/mm2 was evaluated to complete the picture. RESULTS: FAD was associated with a higher number of MC before flea exposure and with a significant increase of eosinophils after flea exposure as compared to non-allergic dogs. The number of IgE+ cells was higher in allergic dogs before and after flea exposure. In allergic dogs mRNA for most cytokines and proteases tested was higher before flea exposure than after flea exposure. After exposure to fleas an increased mRNA production was only observed in non-allergic dogs. In vitro stimulation with flea antigen resulted in a decreased expression of most cytokines in allergic dogs before flea exposure. In contrast, in PBMC, only increased levels of IL-4 and IL-5 mRNA were observed in allergic dogs before flea exposure. However, after flea exposure and additional stimulation with flea antigen the production of mRNA for all cytokines tested was significantly increased in allergic dogs. CONCLUSION: We demonstrated that the response in biopsies and PBMC is different and that FAD is associated with a TH2 response.     

Effect of topical application of fipronil in cats with flea allergic dermatitis

OBJECTIVE: To determine whether topical application of a 10% fipronil solution would control signs of flea allergic dermatitis in cats housed under natural conditions. DESIGN: Multicenter open clinical trial. ANIMALS: 42 client-owned cats with flea allergic dermatitis. PROCEDURES: Study cats along with all other cats and dogs living in the same houses were treated with 10% fipronil solution topically on days 0, 30, and 60. Flea counts and clinical assessments were performed on study cats on days 0, 14, 30, 60, and 90. RESULTS: Percentage reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared with day-0 geometric mean count, were 75, 73, 85, and 94%, respectively. Pruritus score was significantly improved at each examination after day 0, and pruritus was reduced or eliminated in 31 of 40 (78%) cats at the final examination. Similarly, scores for severity of miliary dermatitis and alopecia were significantly improved at each examination, except for alopecia score on day 14. Overall treatment efficacy, assessed on day 90, was excellent for 28 (70%) cats, good for 6 (15%), moderate for 3 (7.5%), and poor for 3 (7.5%). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that monthly topical application of fipronil is effective for treatment of flea allergic dermatitis in cats housed under natural conditions.     

Measurement of serum immunoglobulin E (IgE) specific for house dust mite antigens in normal cats and cats with allergic skin disease

The purpose of this study was to determine whether cats with allergic skin disease have significant concentrations of serum Immunoglobulin E (IgE) specific for antigens derived from the house dust mites (HDM) Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP). Enzyme-linked immunosorbent assays (ELISA) were developed for this purpose. Binding of serum allergen-specific IgE was detected via the use of biotinylated Fc-epsilon receptor alpha chain protein (FcvarepsilonRIalpha). Following optimisation of the assay, serum samples from 59 cats with allergic skin disease and 54 clinically normal cats were screened. Results were expressed as ELISA units per ml (EU/ml) compared to a standard curve. Serological findings were correlated with the clinical presentation of affected cats. Cats with symptoms of feline allergic skin disease were grouped as follows: self-induced alopecia without lesions (group 1), papulocrusting dermatitis (group 2), eosinophilic granuloma complex (group 3), papular/ulcerative dermatitis of head and neck/facial dermatitis (group 4), and a combination of symptoms (group 5). Control normal cats comprised the final group (group 6). The Kruskal-Wallis test was used for statistical analysis. There was no significant difference between groups for DF- and DP-specific IgE concentrations with a p-value of 0.875 and 0.705, respectively. Although the FcvarepsilonRIalpha-based ELISA was able to detect house dust mite-specific feline IgE, the presence of this allergen-specific IgE correlates poorly with the presence of clinical manifestations of allergic skin disease. The results of this study question the clinical relevance of house dust mite-specific IgE in feline allergic skin disease.     

The immunopathogenesis of flea allergy dermatitis in dogs, an experimental study

In this study, we investigated the development of clinical disease and immune responses in the development of an experimental model of flea allergy dermatitis. Dogs were randomly divided into four treatment groups and were infested with fleas on two different feeding schedules (continuous and episodic). Group 1 consisted of four non-exposed dogs (negative controls) and Group 2 consisted of six dogs exposed to fleas continually. Groups 3 and 4 consisted of 14 dogs each that were exposed to fleas on an episodic schedule (two consecutive days every other week for 12 weeks). Group 4 also received intraperitoneal injections of a low dose of lectin (ricin) with immunomodulatory properties. The purpose of Group 4 was to investigate the effects of ricin on enhancing the development of clinical signs, flea antigen-specific IgE levels and altering the number of CD4+ and CD8+ T cell subsets in peripheral blood. Clinical signs developed in all flea exposed dogs, however, the dermatology lesion scores were less and shorter in duration for continuously exposed dogs compared to episodic exposed dogs, independent of ricin treatment. Lesion development was concentrated in the flea triangle and consisted principally of erythema, followed by alopecia, excoriation, papules, and crusts. CD4+ and CD8+ lymphocyte subsets or IgE levels were not altered by ricin treatment. Flea antigen-specific IgE values were highest in dogs exposed to fleas on a continuous basis compared to those episodically exposed. A greater percentage of clinical responder dogs with negative flea-specific IgE titers or negative intradermal test (IDT) were present in the episodic exposure groups than in the continuous exposure group. IgE titers corresponded slightly better with clinical responders than the IDT. The agreement between the IgE titers and IDT was good (weighted K = 0.67). Histopathology of skin samples were consistent with a Type I hypersensitivity. In conclusion, we were able to develop a model of flea allergy dermatitis by experimentally exposing dogs to fleas on an episodic and continuous feeding schedule. In this study, continuously exposed dogs did not develop immunotolerance, and ricin did not enhance the development of FAD.     

Immediate intradermal flea antigen reactivity in clinically normal adult dogs from south Florida, USA

Eighty-six clinically normal adult dogs from southern Florida, USA, with no history of dermatitis, were intradermally skin tested with Greer flea antigen 1:1000 w/v to determine the prevalence of positive immediate intradermal reactivity. This study describes the test group of animals and reports the prevalence of sensitivity to the Greer whole-body flea antigen in normal dogs living in a flea-rich environment. Similar to previous research, the highest prevalence of reactivity to flea antigen occurred at 3–4 years of age. The results indicate that 24% of clinically normal dogs from a flea-rich environment exhibited positive immediate skin test reactivity. These dogs had no clinical signs of flea allergic dermatitis (FAD) in spite of ongoing flea exposure. A 2-year follow-up telephone call to the owners of these flea antigen intradermal skin test (IDST)-positive dogs indicated that only two of 21 dogs had developed clinical signs of FAD.     

Serum immunoglobulin E concentrations in West Highland White Terrier puppies do not predict development of atopic dermatitis

Sera from 154 West Highland White Terrier puppies between 6 and 12 weeks of age were assayed for total IgE using a sandwich ELISA method. Development of clinical signs of atopic dermatitis in these dogs was monitored by use of an annual owner questionnaire, until the dog reached 3 years of age. Of 114 evaluated dogs, skin disease severe enough to warrant veterinary examination was reported in 52 (46%) during the three study years. A diagnosis of atopic dermatitis was made by the attending veterinarian in 28 dogs (25%). Certain litters had an especially high prevalence of apparently atopic dogs, consistent with the genetic predisposition towards atopy in this breed, but clear evidence of consistent heritability was not present. The median IgE concentration in 154 puppies at 6–12 weeks of age was 0.9 units mL⁻¹, with a skewed distribution. Significant ( P < 0.01) variation in serum IgE concentrations was observed between litters, with median serum IgE concentrations for a litter ranging from 0 to 27.7 units mL⁻¹. The median serum IgE concentration in puppies that later developed clinical signs of atopic dermatitis was not significantly different from that of puppies that remained healthy. There were no apparent correlations or significant differences found between serum IgE concentration as a puppy, parental history of skin disease, and subsequent emergence of clinical signs of atopic dermatitis. We conclude that early total serum IgE determinations seem to have little usefulness in predicting the later onset of atopic dermatitis in this breed.     

IgE and IgG antibodies in skin allergy of the horse

In horses, allergies have been characterized by clinical signs and/or intradermal (i.d.) allergen testing. Our aim was to find the first direct evidence that immunoglobulin E (IgE) mediates equine allergy. In addition, we tested the hypothesis that immediate skin reactions in horses can also be mediated by IgG. Anti-IgE affinity columns were used to purify IgE from serum of one healthy horse and three horses affected with summer eczema, an allergic dermatitis which is believed to be induced by Culicoides midges. A modified Prausnitz-Küstner experiment was performed in four clinical healthy horses by i.d. injection of the purified serum IgE antibodies. The following day, Culicoides allergen was injected at the same sites. Skin reactions were not observed in response to allergen alone, and in two horses after stimulation at any previous IgE injection site. However, the other two horses showed an immediate skin reaction at the previous injection sites of IgE obtained from allergic horses. In addition, purified monoclonal antibodies to various equine immunoglobulin isotypes were injected i.d. into six healthy horses. Immediate skin reactions were observed in response to anti-IgE (6/6 horses) and anti-IgG(T) injections (5/6 horses). The specificities of both antibodies for IgE and IgG(T), respectively, were confirmed by enzyme linked immunosorbent assays. The results provide the first direct evidence that IgE mediates classical Type-I allergy in horses and plays a major role in the pathogenesis of summer eczema. The data also suggest that IgG(T) can bind to skin mast cells and might contribute to clinical allergy.     

Diagnosis of flea allergy dermatitis: comparison of intradermal testing with flea allergens and a FcepsilonRI alpha-based IgE assay in response to flea control

The objective of this study was to evaluate the accuracy of in vivo and in vitro tests in the diagnosis of flea allergy dermatitis in comparison with history, clinical signs and response to flea control. Intradermal testing using four different sources of flea allergens and FcepsilonRIalpha-based immunoglobulin (Ig)E assays were performed in 15 flea-allergic dogs, 15 atopic dogs and 15 dogs infested with fleas but showing no clinical signs of skin disease. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were calculated for all five tests and results varied greatly. Sensitivity, specificity and overall accuracy were 27, 83 and 64%, respectively, for one extract (Isotec), 67, 90 and 82% for another extract (Greer), 93, 90 and 91% for flea saliva, 40, 90 and 73% for the recombinant Cte f 1 both produced by Heska Corp. and 87, 53 and 64% for a FcepsilonRIalpha-based IgE assay. These results indicate that intradermal testing with flea extracts is more accurate in the diagnosis of flea allergy dermatitis than in vitro tests. Moreover, pure flea saliva used as a reagent for intradermal testing provided the best results in terms of sensitivity, specificity and overall accuracy although the Greer extract, a whole body flea extract, also allowed a good correlation between intradermal testing results and clinical approach to flea allergy dermatitis diagnosis.     

Evaluation of fipronil spot-on in the treatment of flea allergic dermatitis in dogs

The purpose of this study was to evaluate the effectiveness of treatment with 10 per cent fipronil solution for controlling signs of flea allergic dermatitis in dogs under field conditions. Thirty-one client-owned dogs with flea allergic dermatitis were treated with three monthly applications of 10 per cent fipronil solution. Flea counts and pruritus were significantly reduced at all post-treatment visits. At the final visit, on day 90, flea counts were reduced by 98 per cent, and pruritus was reduced or eliminated in 84 per cent of the study dogs. Dermatological lesion scores for erythema, crusts, scales and papules were also significantly improved by the final visit. The overall assessment of efficacy on day 90 was 'excellent' to 'good' for 87 per cent of the study dogs. The results demonstrate that treatment with monthly topical applications of 10 per cent fipronil solution is effective in reducing the prevalence and severity of signs of flea allergic dermatitis in dogs.     

Double-blind flea hyposensitization trial in cats

In a double-blind clinical trial, flea antigen was injected subcutaneously or intradermally in cats with signs of fleabite allergic dermatitis. No significant clinical improvement was noted by the investigator or the owner in either antigen-treated or control groups over a 20-week period.     

IgE and IgG antibodies to flea antigen in differing dog populations

A radioimmunoassay was developed for the detection of IgG and IgE canine antibodies against partially purified flea antigen. Low background levels were found in flea naive dogs, but high levels of both IgE and IgG antibodies were found in many sera from dogs with clinical flea hypersensitivity. In sera from non-allergic dogs exposed chronically to fleas, IgE levels differed little from background, and levels of IgG anti-flea antibodies were much lower than those from the flea allergic group. The results suggest that chronic flea exposure may result in partial or complete tolerance rather than hyposensitization in the commonly accepted sense.     

The effect of multigenerational diet containing genetically modified triticale on immune system in mice

The safety assessment of genetically modified (GM) food and feed is performed to identify the possible effects upon animal and human health, also the long-term, multigenerational influence upon functioning of different organs and systems, such as the immune system. In this study C57BL/6J mice were fed for five consecutive generations with pellets containing 20% of conventional triticale grain (control) vs. pellets containing 20% of the transgenic triticale grain resistant to BASTA herbicide (experimental). The F5 experimental animals showed enlarged inguinal and axillary lymph nodes, but not spleens, and increased WBC counts in blood (but within the norm for Mus musculus). Immunophenotyped cell suspensions derived from spleens, inguinal and axillaris lymph nodes and PBMCs from blood showed the significant decrease in the percentage of T cells in spleen and lymph nodes and the B cells in lymph nodes and blood of the F5 experimental mice in comparison to the control F5 mice. Immunoblotting analysis of IL-2, IL-4, IL-10, IL-12, IL- 6, IFN-gamma levels in serum showed significantly increased IL-2 levels and decreased IL-6 levels in the F5-experimental mice sera. No significant changes in the levels of IgE in sera in both mice groups were observed. The obtained results indicate that multigenerational use of feeds for rodents containing the GM-triticale leads to expansion of the B cell compartment in the secondary lymphoid organs, but it is not caused by malignant processes or the allergic response.     

Atopy.

Atopy should be considered an immunological disorder that may result in several clinical conditions including respiratory disease, allergic dermatitis, food allergy dermatitis, and perhaps flea allergy dermatitis. The clinical course of the disease tends to fluctuate from season to season, which makes objective evaluation of injection therapy difficult. The disease is subject to both familial and environmental influences, and dogs maintain the atopic state throughout their life. The disease cannot be cured; however, a combination of symptomatic and specific injection therapy usually provides adequate control of the clinical signs. Owners of atopic dogs should appreciate that their pet has inherently itching skin, a cure for which is unlikely to be found.     

Interleukin-6 is produced during both murine and avian Eimeria infections

The production of interleukin-6 (IL-6) during Eimeria infection was investigated in an attempt to gain a better understanding of the role of this multi-functional cytokine in resistance to this parasite. IL-6 production was measured in both chickens, in which the disease is of economic importance, and the better-characterised murine model system.Systemic and local IL-6 production in mice during E. vermiformis infection was investigated, in the relatively resistant BALB/c strain, and the relatively susceptible C57 BL/6 strain, using a murine IL-6 ELISA and the 7TD1 assay. Enhanced systemic production of IL-6 in serum was seen in infected BALB/c mice when compared to C57 BL/6 mice. This difference was also reflected in the draining lymph node of the site of infection, assessed by testing supernatants from stimulated mesenteric lymph node cells taken from infected mice at different times post-infection.Production of chicken IL-6-like factor activity was investigated using a murine IL-6 7TD1 bioassay. The presence of substantial quantities of IL-6-like factor activity was detected in serum taken from some chickens infected with E. tenella during the course of primary infection and, in a separate experiment, during the first few hours post-infection, a time when the pro-inflammatory capacity of IL-6 would influence the developing immune response. These results suggest that IL-6 is also important in the induction of immune effector responses to Eimeria infections in the chicken.     

Canine atopic dermatitis in Greece: clinical observations and the prevalence of positive intradermal test reactions in 91 spontaneous cases.

Atopic dermatitis was diagnosed in a total of 91 dogs by combining the compatible historical evidence and clinical signs with the presence of one or more positive intradermal test reactions well correlated with the exposure to the aeroallergens and the seasonality of the clinical signs. Compared to the general hospital population Yorkshire terriers, Chinese Shar-Peis and cocker spaniels showed a strong predilection. No such predilection was found regarding the sex of the animals. The age of the dogs at the onset of the clinical signs ranged from 2 months to 8 years (median: 2.5 years). Moderate to severe pruritus, noticed in all the 91 dogs, was either localized (29/91) or generalized (64/91) and non-seasonal (43/91), seasonal (19/91) or of unknown seasonality (29/91). The most common cutaneous lesions included erythema, hyperpigmentation, hypotrichosis and crusts; their body distribution was generalized (64%) or localized (36%) with the feet as the most common site of involvement. Five dogs that had unlesional skin were significantly younger and had been pruritic for a shorter period of time compared to the majority of our study population. Otitis externa (43/91) and bacterial pyoderma (30/91) were the most common conditions associated with atopic dermatitis, while the prevalence of Malassezia dermatitis was very low (2/91). Of the other allergic skin diseases flea allergic dermatitis was the most common (29/91) followed by food hypersensitivity (2 out of the 15 dogs tested). The majority of the dogs demonstrated multiple sensitivities to the 50 aeroallergens tested, while domestic mites (77/91), and particularly Dermatophagoides farinae (64/91), were the most commonly implicated. The total number of the positive intradermal test reactions was increasing parallel to the age of the dogs but it was negatively associated with the presence of skin lesions on the carpal and tarsal joints.     

Canine atopic dermatitis: a retrospective study of 266 cases examined at the University of California, Davis, 1992-1998. Part I. Clinical features and allergy testing results

The medical records of 266 dogs diagnosed as having atopic dermatitis were reviewed. Statistical data were evaluated referable to breed predilections, clinical signs and positive reactions to allergens. Positive reactions were most common to house dust mites (more common with clinical signs in the fall) followed by moulds (more common with clinical signs in the fall and spring). Dogs with positive reactions to moulds, trees or cultivated plants were more likely to have skin and ear yeast infections. Dogs with positive reactions to cultivated plants were more likely to have otitis externa and pedal lesions. Positive reactions to house dust were more common in dogs with early onset of signs and in those tested early in the disease. Dogs had more positive reactions to weeds when allergy tests were performed in the summer and fall. Positive reactions to flea antigen were highly correlated with the clinical diagnosis of flea allergy dermatitis.     

Prospective open pilot study on the use of ciclosporin for feline allergic skin disease

OBJECTIVES: To evaluate the efficacy of ciclosporin in cats with allergic skin disease. METHODS: Ten cats with signs of allergic skin disease were administered ciclosporin daily at a dose of 3.6 to 8.3 mg/kg for one month. None of these cats had previously responded to a hypoallergenic diet trial, and all animals had previously been treated with endectoparasiticidal drugs, with no improvement two weeks before entering the trial. On days 0 and 30, owners assessed pruritus with a visual analogue scale, and veterinarians evaluated cutaneous lesions. RESULTS: All the cats had pruritus and erythema, five had alopecia, two had an eosinophilic plaque, one had miliary dermatitis and two had both alopecia and an eosinophilic plaque. Good or excellent improvement was observed in 40 per cent of cats for pruritus, 57 per cent of cats for alopecia and 60 per cent of cats for erythema. A significant decrease in mean scores was observed for pruritus only, while for erythema and alopecia, it was close to being significant (P < 0.052). CLINICAL SIGNIFICANCE: Ciclosporin may be helpful in symptomatically treating signs of feline allergic skin disease. However, it is important to remember that ciclosporin is not licensed for use in cats.     

Fundamentals of host immune response against Brucella abortus: what the mouse model has revealed about control of infection

The studies reviewed here evaluated the role cellular immune system components play in control of brucellosis by conducting comparative studies with brucella-resistant C57BL/10 or C57BL/6 mice and susceptible BALB/c mice. We have shown by both in vitro and in vivo studies that activation of macrophages with interferon-gamma (IFN-γ) is an important factor for control of infection with B. abortus in the mouse model and that the mechanism of anti-brucella activity largely involved reactive oxygen intermediates. Differences in control of the organism by resistant and susceptible mice was not related to inherent differences in the ability of their macrophages to control infection either with or without IFN-γ activation nor was it attributable to NK cells since we found no role for them in control of brucellosis in either mouse strain. However, relative resistance to brucellosis did correlate with increased production of IFN-γ by CD4 T cells during the first weeks after infection while IL-10 contributed to susceptibility in BALB/c mice. Moreover, by 3 weeks post-infection splenocytes from the susceptible BALB/c mice failed to produce IFN-γ and relied on TNF- as well as CD8 T cells to control infection until the end of the plateau phase around 6 weeks post-infection when IFN-γ production resumed and clearance began. In contrast, IFN-γ was crucial for control throughout the infection in the more resistant C57BL/6 mice and the mice died in its absence by 6 weeks post-infection compared to 12 weeks for the more susceptible mice that relied on additional mechanisms of control. In contrast to the IFN-γ knock-out mice, both β2 microglobulin knock-out C57BL/6 mice, which do not express conventional MHC class I molecules and thus cannot present antigen to CD8 T cells, or perforin knock-out C57BL/6 mice, which have no T cell cytotoxic activity, controlled and cleared the infection as well as normal C57BL/6 mice. The hiatus of IFN-γ production in BALB/c mice correlated with very high levels of total IL-12 and it was postulated that the lack of IFN-γ was a consequence of p40 homodimer blocking activity. However, reduction of p40 IL-12 in vivo through administration of indomethacin reduced the infection without a concomitant measurable increase in IFN-γ. Current studies are aimed at elucidating the mechanism of the IFN-γ hiatus.     

Optimization of the use of C57BL/6 mice as a laboratory animal model for Neospora caninum vaccine studies

The development and testing of vaccines for Neospora caninum in mice require challenge studies to demonstrate a reduction in clinical signs or prevention of vertical transmission of the parasite after vaccination. Genetic susceptibility to N. caninum varies with the strain of mice. In this study, C57BL/6 mice were evaluated as a model for Neospora vaccine studies. A lethal challenge model was developed and the LD(50) was determined to be 1.5 x 10(7)N. caninum tachyzoites/mouse, delivered intraperitoneally. Brain lesions encountered in sections from sub-lethally challenged mice were scored on the basis of severity and total number of lesions to develop a histopathological scoring system for vaccine efficacy. A vertical transmission model for N. caninum vaccine studies was developed by studying mice that were infected either 2 weeks prior to mating or between days 12 and 14 of pregnancy. It was found that infection prior to mating reduced the average number of pups per litter. DNA extracted from fetal tissue was examined by a N. caninum specific polymerase chain reaction (PCR). The rate of vertical transmission was 0, 100 and 90.5% for the uninfected controls, mice infected during pregnancy and mice infected before mating, respectively. This study demonstrates that the C57BL/6 strain of mice is a good model for N. caninum vaccine studies because it is possible to establish a clear-cut lethal challenge model in C57BL/6 mice and they transmit the disease to their offspring efficiently.     

Ultrastructural findings of feline eosinophilic dermatoses

The objectives of this multicentre study were to describe demographics and clinical findings of a group of 63 dogs with nonseasonal atopic dermatitis (AD), where concurrent flea allergy dermatitis, ectoparasite infestation, food adverse reactions and secondary infections had been ruled out. The breed, sex, age of onset, distribution of skin lesions, prevalence of otitis externa, secondary skin infections and additional noncutaneous clinical signs were recorded. A veterinarian recorded skin lesions from 15 different body regions. Each body region was scored according to degree of erythema, alopecia, excoriations, scale, crusts, lichenification and hyperpigmentation that was present. An early age of onset (37% of the dogs being less than 1 year old) was more common in this group of dogs than described in the literature. The German shepherd breed was over-represented (21% as compared with 7–9.9% of the veterinary clinic population) and approximately half of the German shepherd dogs (46%) started showing clinical signs before 1 year of age. Erythema was the overall most common type of skin lesion, with facial erythema and conjunctivitis being less commonly reported than in other studies. Feet, ears and groin were the most common sites for skin lesions. This study indicates that it is not uncommon for dogs with nonseasonal AD to have the onset of clinical signs start at a younger age (less than 1 year of age) and have clinical lesions that vary from previously published reports. This discrepancy might be allergen-dependent or breed-related.
  The study was funded by Boehringer Ingelheim Vetmedica, Denmark.