Figurate erythema in 11 Eastern European sphynx cats.

BACKGROUND: In humans, figurate erythema (FE) represents a heterogenous group of dermatoses with circular or serpiginous erythematous skin lesions; FE has not been reported in cats. OBJECTIVES: To report clinical and histological characteristics and outcomes of FE in sphynx cats from Baltic sea-bordering countries. ANIMALS: Eleven client-owned sphynx cats with FE. MATERIALS AND METHODS: We recruited cases meeting the following criteria: (i) a sphynx breed, (ii) FE with or without scaling, (iii) a chronic, waxing-and-waning course lasting longer than a month and (iv) an absence of other skin diseases. RESULTS: Of 11 cats, there were seven Donskoys, one Peterbald, one Ukrainian Levkoy and two presumed Canadian sphynxes; all except one were males, and the age of onset was <12 months in eight cats. Skin lesions lasted between 1.2 and 56 months, and they consisted of erythematous plaques with a linear-to-serpiginous, annular, gyrate or iris configuration predominating on the trunk and extremities. Scaling was often seen trailing the edge of the centrifugally expanding erythema. All cats were otherwise asymptomatic or mildly pruritic. Dermatophytosis was ruled out by special stains and/or fungal cultures in eight cats. Microscopic lesions revealed focal, mild-to-moderate epidermal hyperplasia and hyperkeratosis, minimal-to-mild dysplasia and subepidermal collagen smudging. Special stains were negative for dermatophytes. The clinical remission of FE was not achieved with diet changes or medical interventions; yet, a spontaneous, transient, partial or complete improvement occurred in most cats. CONCLUSION AND CLINICAL RELEVANCE: This is the first report of FE in sphynx cats from Eastern Europe.

Spontaneous autoimmune subepidermal blistering diseases in animals: a comprehensive review.

Autoimmune subepidermal blistering diseases (AISBDs) are rare skin disorders of animals that were first identified in dogs but several AISBDs are now recognised in other companion animal species. Most AISBDs in animals are homologues of the human diseases and are thought to share similar pathomechanisms of epidermal and/or mucosal blister formation caused by autoantibodies targeting structural proteins of the basement membrane zone (BMZ). Disruption of their structural function by the autoantibodies and/or recruited inflammation leads to BMZ fragility, which presents clinically as vesicles, bullae and, later, deep erosions and ulcers. Canine AISBDs are the best characterised, particularly the more common variants such as mucous membrane pemphigoid (48%), epidermolysis bullosa acquisita (EBA) (26%), and bullous pemphigoid (10%). Exceedingly rare AISBDs in the dog are junctional EBA, mixed AISBD, type-1 bullous systemic lupus erythematosus, linear IgA dermatosis, and pemphigus gestationis. The diagnosis of a specific AISBD is made by combining the clinical features (breed, age, lesion distribution) with histological evidence of subepithelial clefting, but not all AISBDs can be differentiated in this manner and specialised immunological testing is required. This latter, unfortunately, is not readily available and, therefore, the specific AISBD diagnosis often remains unconfirmed. While this limits further understanding of these diseases, it does not prevent clinicians from treating their patients, as the treatment approaches are similar for the different AISBDs in dogs. This review primarily focuses on canine AISBDs, the species for which these diseases have been best characterised, and shorter descriptions of variants in other species are also provided.

A randomised controlled trial testing the rebound-preventing benefit of four days of prednisolone during the induction of oclacitinib therapy in dogs with atopic dermatitis.

BACKGROUND: A rebound of pruritus occasionally occurs after oclacitinib dose reduction in dogs with atopic dermatitis (AD). OBJECTIVES: To determine whether an initial 4-day course of prednisolone decreases the probability of a pruritus rebound after reducing the frequency of oclacitinib administration. ANIMALS: Forty dogs with mild-to-moderate AD lesions and moderate-to-severe pruritus. MATERIALS AND METHODS: Dogs were randomised to receive oclacitinib at 0.4-0.6 mg/kg twice daily for 14 days then once daily, alone or with prednisolone at 0.5 mg/kg, orally, twice daily for the first 4 days. Clinicians graded the Canine Atopic Dermatitis Extent and Severity Index (CADESI)4 and 2D-investigator global assessment (IGA) before and after 28 days; owners assessed the pruritis Visual Analog Scale (PVAS)10 and Owner Global Assessment of Treatment Efficacy (OGATE) on Day (D)0, D4, D14, D21 and D28. We considered a rebound any increase greater than one PVAS10 grade at D21 compared to D14. RESULTS: On D21, there were significantly fewer rebounds in the dogs receiving prednisolone (three of 20, 15%) compared to those given oclacitinib alone (nine of 20, 45%; Fisher's test, p = 0.041). Compared to oclacitinib monotherapy, the concurrent administration of prednisolone for the first 4 days led to significantly lower PVAS10 on D4 and D28, CADESI4 and 2D-IGA on D28, and OGATE on D21 and D28 (Wilcoxon-Mann-Whitney U-tests). Adverse effects of therapy were minor, intermittent and self-resolving. CONCLUSIONS AND CLINICAL RELEVANCE: The initial addition of 4 days of prednisolone significantly decreased the probability of a rebound of pruritus 1 week after oclacitinib dose reduction. This short concomitant glucocorticoid administration led to a higher skin lesion improvement and improved perception of treatment efficacy with minimal adverse effects.

Effective treatment of canine chronic cutaneous lupus erythematosus variants with oclacitinib: Seven cases.

BACKGROUND: The treatment of canine chronic cutaneous lupus erythematosus (CCLE) variants generally requires immunosuppression, which often results in potentially severe adverse effects. Janus kinase inhibitors, like oclacitinib, might be a valuable treatment option due to their rapid inhibition of the action of interferons known to be relevant in the pathogenesis of CCLE. OBJECTIVES: To report the efficacy and safety of oral oclacitinib for the treatment of canine CCLE variants. ANIMALS: Seven dogs were diagnosed with CCLE based on clinical signs and compatible histopathological findings. MATERIALS AND METHODS: Oclacitinib was administered at the induction dosage of 0.45 mg/kg twice daily to 1.8 mg/kg once daily. The response to treatment was graded as 'good' when there was ≥50% lesion reduction, or as 'complete remission' if all active lesions had resolved. Complete blood counts were performed at variable intervals. RESULTS: A complete remission of all lesions was obtained in the dog with exfoliative cutaneous lupus erythematosus, both dogs with mucocutaneous lupus erythematosus and three of four dogs with facial discoid lupus erythematosus (FDLE); a good response was seen in the remaining dog with FDLE. The first visible improvement of signs was seen within 2-to-3 weeks, while the time to complete remission was around 2 months. Clinical adverse effects were not seen, and haematological parameters remained within the reference range. CONCLUSIONS AND CLINICAL RELEVANCE: Oclacitinib may be considered an effective treatment option for different variants of canine CCLE.

Cytokine transcriptome profiling in acute experimental canine atopic dermatitis skin lesions after IL-31 inhibition with lokivetmab.

BACKGROUND: The caninised monoclonal antibody lokivetmab (LKV), directed at interleukin (IL)-31, is very effective at controlling pruritus in most dogs with atopic dermatitis (AD). However, evidence exists that IL-31 is not required for the induction of acute allergic skin inflammation, which might explain why this treatment is less efficacious in some dogs with AD. HYPOTHESIS/OBJECTIVES: To compare the comprehensive transcriptome analysis of house dust mite (HDM)-sensitised dogs with and without treatment with LKV to attest our hypothesis that LKV does not majorly affect acute cytokine/chemokine production. ANIMALS: Six HDM-sensitised atopic Maltese-beagle dogs. MATERIALS AND METHODS: In this cross-over study, the cytokine profiling of acute AD skin lesions was compared by RNA sequencing (RNA-Seq), with or without LKV-induced inhibition of IL-31. Skin biopsies were obtained from each dog at 0, 6, 12, 24, 48, and 96 h after epicutaneous HDM allergen provocation. RESULTS: Macroscopic and microscopic skin lesion scores were not significantly different between the LKV- and nontreatment groups at any time points. Likewise, the results of RNA-Seq analysis revealed no significant difference in the messenger (m)RNA expression of the major cytokines between these two groups. In LKV-treated dogs, IL6, IL9, IL13, IL33, CCL17, and CCL22 were significantly upregulated compared to their baseline expression levels, suggesting that these cytokines are unaffected by IL-31 inhibition. CONCLUSIONS AND CLINICAL RELEVANCE: IL-31 inhibition is insufficient to prevent the expression of other proinflammatory mediators in acute AD and these could be considered as other potential therapeutic targets.

Histopathological characterisation of trunk-dominant canine pemphigus foliaceus, and comparison with classic facial and insecticide-triggered forms.

BACKGROUND: While the clinical features were described recently, the histopathological characterisation of trunk-dominant canine pemphigus foliaceus (PF) is lacking, and whether it differs from classic facial or insecticide-triggered PF is unknown. HYPOTHESIS/OBJECTIVES: This study describes the histopathological findings of trunk-dominant PF, and compares the results to classic facial and insecticide-triggered PF. ANIMALS: Skin biopsies from 103 dogs with clinically characterised trunk-dominant (n = 33), classic facial (n = 26) and insecticide-triggered PF (n = 44) were included. MATERIALS AND METHODS: Histological sections, randomised and blinded, were scored for over 50 morphological parameters of pustules, epidermis, dermis, adnexa and crusts. Intact pustule area and width were measured by digital microscopy. RESULTS: In trunk-dominant PF, 77 intact pustules were predominantly subcorneal (0.0019-1.940 mm2 area, 0.0470-4.2532 mm wide), and contained from one to over 100 acantholytic keratinocytes. Pustules had boat acantholytic cells, corneocytes, perinuclear eosinophilic rings, neutrophil rosettes, acantholytic cell necrosis, rafts, cling-ons and/or eosinophils. Peripustular epidermal spongiosis, necrosis and lymphocyte exocytosis occurred, as did follicular pustules. Mixed dermal inflammation often contained eosinophils. Trunk-dominant PF did not differ from the other PF groups except for few parameters, such as having fewer rafts (p = 0.003). Additional autoimmune inflammatory patterns occurred in all PF groups. CONCLUSIONS AND CLINICAL RELEVANCE: Trunk-dominant PF and other canine PF variants are histologically similar, which indicates shared pathomechanisms. The identification of common boat acantholytic cells and corneocyte separation has implications for the mechanisms of acantholysis. The diversity of histopathological and polyautoimmunity features support complicated immune mechanisms. Finally, results indicate that diagnostic biopsies cannot differentiate between these PF variants in dogs.

Hyperkeratotic erythema multiforme variant in 17 dogs.

BACKGROUND: A new canine subgroup defined as 'old-dog' or 'hyperkeratotic' erythema multiforme (HKEM) with marked hyperkeratosis and parakeratosis has been proposed without any detailed description of larger case series. OBJECTIVES: We report herein the signalment, clinical signs, treatment outcome, and histopathological and immunological findings in 17 dogs with HKEM. ANIMALS: Inclusion criteria were the presence of (i) scaly skin lesions with or without crusting; and (ii) microscopic lesions typical of EM (i.e. a panepidermal cytotoxic lymphocytic dermatitis with or without basal keratinocyte apoptosis); and (iii) microscopic ortho- and/or parakeratotic hyperkeratosis affecting the interfollicular epidermis. MATERIALS AND METHODS: Clinical questionnaires and skin biopsies were reviewed. Polymerase chain reactions for epidermotropic viruses and direct immunofluorescence were performed. RESULTS: Various breeds were affected with an over-representation of males in their mid-to-late adulthood (median age 9 years). Generalised skin lesions included multifocal-to-coalescing, linear and annular macules and plaques with erythema and adherent firm crusting. Microscopic lesions were specific for EM and featured prominent superficial epidermal apoptosis with lymphocytic satellitosis and parakeratosis. No drug triggers were identified. Polymerase chain reactions for canine herpesvirus polymerase gene, canine parvovirus and canine distemper virus were negative in all HKEM and canine erosive EM (15 dogs) biopsies. Lesions failed to respond to oral and/or topical antimicrobials. Complete remission of signs was achieved in 9 of 17 dogs (53%) using immunosuppressive regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Hyperkeratotic erythema multiforme (HKEM) is a chronic, persistent and clinically distinctive erythema multiforme (EM) variant that differs from 'classic' vesiculobullous erosive-to-ulcerative EM in dogs.

Evaluation of native canine skin color by smartphone-based dermatoscopy.

BACKGROUND: Human skin color, predominantly determined by the chromophores of melanin, hemoglobin, and exogenous carotenoids, is often measured to serve various medical and cosmetic applications. Although colorimetry has been used to evaluate the skin erythema in allergic dogs, the native canine skin color remains unknown. METHODS: We measured the skin color in 101 healthy dogs using a calibrated optical system with a smartphone and a mobile dermatoscope DermLite DL1. The results were retrieved in the CIELAB color system and compared to the human color ranges. RESULTS: The lightness (L*) of canine skin ranged from 28.5 to 78.3, which is slightly broader than that of human skin. There was a difference of 3.9 in redness (a*) between canine and human skin, but this variation could be attributed to the similarly valued colorimetric error of the optical system. Nonetheless, the skin yellowness was significantly different for dogs and humans (respective median b* of 12.3 versus 16.6, p < 0.01). This difference might be due to canids not being able to accumulate typically yellowish carotenoids. Furthermore, the native canine skin color did not exhibit a typical dependence between the coordinates of lightness (L*) and yellowness (b*), known as the individual typology angle, °ITA. CONCLUSION: We reported the first dataset of the native canine skin color in the CIELAB color space. We discovered a similarity in skin lightness and a difference in skin yellowness. However, further studies are needed for a more precise comparison of skin redness.

Determination of the efficacy rate and time-to-efficacy of subcutaneous immunotherapy in dogs with atopic dermatitis.

BACKGROUND: Allergen-specific immunotherapy (ASIT) is reported to have a success rate of 50-70% when given for up to 12 months to dogs with atopic dermatitis (AD). How soon ASIT is clinically effective is unclear. OBJECTIVES: To compare the efficacy rate (ER) and time-to-efficacy (TTE) of various types of subcutaneous immunotherapy (SCIT) administered using conventional dosing regimens using the methodology of a critically appraised topic. METHODS AND MATERIALS: Three databases were searched to extract information on the ER and TTE of SCIT in dogs with AD. Herein, "efficacy" was defined as a ≥50% reduction in pruritus and/or skin lesions, and the TTE as the time needed to achieve such a reduction. RESULTS: We selected 12 publications including 194 dogs. The ER was significantly higher with the polymerised allergoids coupled with nonoxidized mannan than for the "classic" aqueous and alum-precipitated SCIT types. A TTE of three months or shorter was seen in a significantly higher proportion of dogs receiving mannan-couple allergoids, pullulan-conjugated Der f 2 or tyrosine-adjuvanted than aqueous or alum-precipitated SCIT; with the latter two formulations, the TTE might be nine months or longer in ≤20% of atopic dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In spite of the low number of articles available for review and small number of enrolled dogs, novel SCIT regimens appear to have a faster - and possibly higher - efficacy than the currently available aqueous or alum-precipitated formulations. A standardisation of outcome measures for ASIT clearly is needed to allow a more meaningful comparison between SCIT types.

Evaluation of the theoretical risk of cross-reactivity among recently identified food allergens for dogs.

BACKGROUND: There is increasing evidence of cross-reactivity between allergens of close or distant species. The A-RISC (Allergens'-Relative Identity, Similarity and Cross-reactivity) index helps evaluate the risk of theoretical cross-reactivity between proteins of the same family among different species. OBJECTIVES: To report the A-RISC indices for several food allergens of dogs between multiple food sources. MATERIALS AND METHODS: We selected several recently characterised food allergens for dogs from fish and chicken (ACTA1, ALDOA, CKM, ENO3, GAPDH, PKM and TPI1), fish (TPM1/2), beef/lamb (PGM1) and corn/potato (WAXY). When quality sequence data were available, A-RISC indices were calculated between multiple animal and plant species that can be used as food sources. For the TPM subunits, A-RISC indices also were calculated with the environmental allergens Bla g 4 and Der f 10, and the Toxocara canis nematode. RESULTS: The A-RISC indices suggest a substantial theoretical risk of cross-reactivity between species for all allergens considered. For TPM, this risk also extends to the environmental and nematode allergens. CONCLUSIONS AND CLINICAL RELEVANCE: There is a high theoretical risk of cross-reactivity between allergens of different species used as food sources. The clinical relevance of these elevated A-RISC indices should be studied further.

An international seroprevalence survey of the IgE sensitisation to the Dermatophagoides farinae house dust mite and two of its major allergens (Der f 2, Zen 1) in atopic dogs.

BACKGROUND: Dogs with atopic dermatitis are often immunoglobulin (Ig)E-sensitised to Dermatophagoides farinae (Df) house dust mites, yet limited data exist on the sensitisation rates to the individual Df allergens, Der f 2 and Zen 1. OBJECTIVES: To determine the IgE sensitisation rates to Df, Der f 2 and Zen 1 in atopic dogs from geographically diverse countries. ANIMALS: Serum was collected from 32 laboratory dogs in Japan, and 837 atopic dogs from 11 countries from five continents: Asia (Japan, Thailand, Taiwan), Europe (Italy, Latvia, the Netherlands, UK), North America (USA), South America (Argentina, Brazil) and Africa (South Africa). METHODS AND MATERIALS: We determined Df-, Der f 2- and Zen 1-specific IgE levels by ELISA. Correlations between the IgE values for these three allergens were calculated. RESULTS: The IgE seropositivity rates for Df varied between 74% (Argentina) and 100% (the Netherlands, Thailand, South Africa), those for Der f 2 between 12% (Argentina) and 88% (South Africa), and for Zen 1 between 70% (Argentina) and 100% (the Netherlands). Apart from the especially low seropositivity rate for Der f 2-specific IgE in Argentina, the percentage of IgE sensitisation varied little between countries. There was significant correlation between the IgE levels to these three allergens which was highest between Df and Zen 1, and lowest between Zen 1 and Der f 2. CONCLUSIONS AND CLINICAL RELEVANCE: The IgE sensitisation to Df is geographically widespread. Der f 2 and Zen 1 are major allergens for dogs in almost all countries where this was evaluated.

Transient and reversible reduction of stratum corneum filaggrin degradation products after allergen challenge in experimentally mite-sensitised atopic dogs.

BACKGROUND: A defective skin barrier occurs in dogs with atopic dermatitis, and there is controversy over whether this defect pre-exists, or is secondary to allergic inflammation. OBJECTIVES: To study if an allergen challenge decreases the natural moisturising factor (NMF), which contains the main filaggrin degradation products. ANIMALS: Four house dust mite (HDM)-sensitised adult atopic dogs from a research colony. METHODS AND MATERIALS: Dogs were challenged epicutaneously with HDMs on the right lateral abdomen while the left thorax served as control. We swabbed the skin surface before, and at days (D)1, D2, D3, D7 and D28 after challenge, on both selected sites; swabs were soaked in detergent and frozen until assayed. The NMF components were measured by liquid chromatography-tandem mass spectrometry (LC/MS-MS). RESULTS: The allergen challenge induced moderate skin lesions at the application sites, and also mild erythema at the control areas. The allergen provocation led to significant decreases in the total NMF and its components trans-urocanic acid (t-UCA), pyrrolidone carboxylic acid (PCA) and serine on both sites. Lesion scores abated by D7 and the NMF concentrations had re-increased by D28. Skin lesion scores correlated negatively with the total NMF, t-UCA and PCA concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: In this experimental model, a single epicutaneous allergen challenge led to a transient and reversible decrease in skin surface NMF and its components, and concentrations were negatively correlated with skin lesion scores. These observations suggest that some of the skin barrier anomalies seen in atopic dogs likely develop secondarily to the underlying cutaneous allergic inflammation.

Identification of major and minor chicken allergens in dogs.

BACKGROUND: Allergens targeted by serum-specific immunoglobulin E (sIgE) in dogs clinically allergic to chicken have not been reported. OBJECTIVES: To characterise the allergens targeted by sIgE in dogs sensitised and allergic to chicken. ANIMALS: Sera from three dogs not sensitised to chicken, from 10 chicken sensitised dogs and from 12 chicken allergic dogs. METHODS AND MATERIALS: Enzyme-linked immunosorbent assay (ELISA) and immunoblotting with a commercial chicken extract were utilized. The bands identified on immunoblotting were sequenced by mass spectrometry for allergen characterization. RESULTS: Using ELISA, we detected chicken-sIgE above the positive threshold in zero of three (0%) nonsensitised dogs, five of five (100%) chicken-sensitised dogs (a selection criterion), and in seven of 12 (58%) chicken-allergic dogs. Immunoblotting performed with the same extract revealed IgE-bound protein bands in 100% of all chicken-sensitised and -allergic dogs, respectively. To identify the allergens, we excised the corresponding bands on the electrophoretic gel, and submitted them for sequencing by mass spectrometry. We conclusively identified seven major allergens (serum albumin, pyruvate kinase M, enolase 3, creatine kinase M, lactate dehydrogenase A, glyceraldehyde-3-phosphate dehydrogenase and triose-phosphate isomerase) and one minor allergen (troponin C), which are relevant to dogs. CONCLUSIONS AND CLINICAL RELEVANCE: We identified herein seven major chicken allergens for dogs, several of which are known to be cross-reactive allergens for humans. Based on their degree of sequence identity, these allergens exhibit the theoretical potential to be cross-reactive between poultry and mammalian meats; six of these allergens already are known to be cross-reactive between chicken and fish species. Future studies should address the clinical relevance and cross-reactivity potential of these chicken allergens in dogs.

Evaluation of Erythema Severity in Dermatoscopic Images of Canine Skin: Erythema Index Assessment and Image Sampling Reliability.

The regular monitoring of erythema, one of the most important skin lesions in atopic (allergic) dogs, is essential for successful anti-allergic therapy. The smartphone-based dermatoscopy enables a convenient way to acquire quality images of erythematous skin. However, the image sampling to evaluate erythema severity is still done manually, introducing result variability. In this study, we investigated the correlation between the most popular erythema indices (EIs) and dermatologists' erythema perception, and we measured intra- and inter-rater variability of the currently-used manual image-sampling methods (ISMs). We showed that the EIBRG, based on all three RGB (red, green, and blue) channels, performed the best with an average Spearman coefficient of 0.75 and a typical absolute disagreement of less than 14% with the erythema assessed by clinicians. On the other hand, two image-sampling methods, based on either selecting specific pixels or small skin areas, performed similarly well. They achieved high intra- and inter-rater reliability with the intraclass correlation coefficient (ICC) and Krippendorff's alpha well above 0.90. These results indicated that smartphone-based dermatoscopy could be a convenient and precise way to evaluate skin erythema severity. However, better outlined, or even automated ISMs, are likely to improve the intra- and inter-rater reliability in severe erythematous cases.

Evaluation of skin erythema severity by dermatoscopy in dogs with atopic dermatitis.

BACKGROUND: To estimate the extent and severity of atopic dermatitis (AD)-related skin lesions, clinical trials enrolling dogs with AD often use categorical scales such as the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and Canine Atopic Dermatitis Lesion Index (CADLI). Despite recent progress in the standardization of these AD-grading scales, the evaluation of the severity of skin lesions (including erythema) remains subjective. OBJECTIVES: To validate an optical set-up with a smartphone and a dermatoscope for the objective estimation of skin erythema severity in atopic dogs. ANIMALS: Forty-three dogs with AD. METHODS AND MATERIALS: An erythema index (EI) was calculated from calibrated skin images and compared to the dermatologist's erythema severity estimate using the erythema grading scale used in the CADESI-04, as well as an ad hoc Visual Analog Scale (VAS) with a continuous palette of red shades. RESULTS: We found a strong correlation based on the Spearman rank correlation coefficient between all erythema valuations: CADESI-04 and VAS: 0.93 [95% CI: (0.85, 0.96)]; CADESI-04 and EI: 0.85 (0.72, 0.92); VAS and EI: 0.82 (0.67, 0.91). There was a good agreement between the objective EI and CADESI-04-based estimates because 71% of samples were classified in the same erythema severity category. When comparing the EI and the VAS, the standard deviation of misestimates was 12% (maximum 100%). CONCLUSIONS AND CLINICAL RELEVANCE: The proposed optical set-up has the potential to make erythema severity estimation objective, thus leading to more reliable AD severity scales for the use in experimental canine AD models or in clinical trials enrolling atopic dogs.

IL-31 and IL-31 receptor expression in acute experimental canine atopic dermatitis skin lesions.

BACKGROUND: To optimise the interleukin (IL)-31-blocking therapy in atopic dermatitis (AD), an understanding of the chronology in the expression of IL-31 and its receptor (IL-31RA) is needed. HYPOTHESIS/OBJECTIVES: (i) To assess the chronological expression of IL-31 in canine AD skin lesions, (ii) to compare it with serum IL-31 levels and macroscopic skin lesion scores, and (iii) to determine the identity of IL-31- and IL-31RA-positive cells. ANIMALS: Four atopic dogs sensitised to house dust mites. METHODS AND MATERIALS: Skin and blood samples were obtained 0 h, 24 h, 48 and 96 h after allergen provocation. IL-31 and IL-31RA single-staining immunofluorescence (IF), as well as IL-31/CD3, IL-31/CD4 and IL-31RA/ß3-tubulin double-staining IF were performed. The IL-31-positive cells were counted subjectively. RESULTS: The peak IL-31 expression for three of four dogs occurred 24 h or 48 h postchallenge; it started to decrease at 96 h. There was no significant correlation between the IL-31 expression scores and the serum IL-31 concentrations or the macroscopic skin lesion scores (P = 0.35 and P = 0.36, respectively). The majority of IL-31-positive cells were positive for CD3 (range 91-100%) and CD4 (range 63-100%), indicating that they were helper T (Th) cells. Unexpectedly, sebaceous glands were strongly immunolabelled with IL-31; the extinction of this positivity after immunoabsorption with IL-31 further supported the validity of this immunostaining. The IL-31RA was visualised on keratinocytes and a small proportion of dermal nerves. CONCLUSIONS AND CLINICAL IMPORTANCE: The early and transient production of IL-31 by Th cells supports the concept of using IL-31 inhibiting strategies as a proactive therapy to prevent flares of AD skin lesions.

Immunopathogenesis of the feline atopic syndrome.

BACKGROUND: Feline diseases of possible allergic origin with similar clinical phenotypes can have a varied underlying pathogenesis. Clinical phenotype, precise aetiology and underlying immunopathogenesis all need to be considered if advances in this neglected area of dermatology are to be made. OBJECTIVES: To document the status of research into the immunopathogenesis of the diseases that fall within the spectrum of the feline atopic syndrome (FAS ), to summarize the conclusions, identify the limitations and recommend future research directions. METHODS AND MATERIALS: A search of the literature was undertaken. The strengths and validity of the data and the contributions to our current understanding of the immunopathogenesis were analysed. Skin diseases of presumed allergic aetiology and asthma were assessed separately, as was the role of antibodies, cells and cytokines in each. RESULTS: The research varied in its quality and its impact often was limited by a failure to employ strict criteria in case selection. This reflected the difficulties of skin reaction patterns associated with a number of inciting causes. Research into feline asthma was handicapped by the difficulties of investigating clinical material, and much of the useful information was derived from experimental models. CONCLUSIONS AND CLINICAL IMPORTANCE: The evidence reviewed was supportive of a role for immunoglobulin (Ig)E in the pathogenesis of both feline atopic skin syndrome (FASS) and asthma, albeit not strongly so. The inflammation noted in both FASS and asthma is accompanied by eosinophils and lymphocytes, and these findings, together with the cytokine expression, are suggestive in some (not all) cats of T-helper type 2 immune dysregulation.

Feline allergic diseases: introduction and proposed nomenclature.

BACKGROUND: Feline allergic diseases present as challenging problems for clinicians, not least because of the number of reaction patterns of the feline skin, none of which are specific for allergy. Furthermore, there is some controversy over the nomenclature that should be used in their description. OBJECTIVES: To review the literature, assess the status of knowledge of the topic and the extent to which these diseases could be categorized as atopic in nature, and make recommendations concerning nomenclature. METHODS: Atopic diseases in humans and cats were researched. A comparison then was made of the essential features in the two species. RESULTS: There were sufficient similarities between human atopic diseases and the manifestations of feline diseases of presumed allergic aetiology to justify the use of "atopic" to describe some of the feline conditions affecting the skin, respiratory and gastrointestinal tract. However, none of the allergic skin diseases showed features consistent with atopic dermatitis as described in man and the dog. CONCLUSIONS AND CLINICAL IMPORTANCE: The term "Feline Atopic Syndrome" (FAS) is proposed to encompass allergic diseases of the skin, gastrointestinal tract and respiratory tract, and "Feline atopic skin syndrome" (FASS) proposed to describe allergic skin disease associated with environmental allergies. We are not aware of any adverse food reactions in cats that are attributable to causes other than immunological reactions against the food itself. We therefore propose an aetiological definition of "Food Allergy" (FA) to describe such cases.

Malassezia species dysbiosis in natural and allergen-induced atopic dermatitis in dogs.

Malassezia dermatitis and otitis are recurrent features of canine atopic dermatitis, increasing the cost of care, and contributing to a reduced quality of life for the pet. The exact pathogenesis of secondary yeast infections in allergic dogs remains unclear, but some have proposed an overgrowth of M. pachydermatis to be one of the flare factors. The distribution of Malassezia populations on healthy and allergic canine skin has not been previously investigated using culture-independent methods. Skin swabs were collected from healthy, naturally affected allergic, and experimentally sensitized atopic dogs. From the extracted DNA, fungal next-generations sequencing (NGS) targeting the ITS region with phylogenetic analysis of sequences for species level classification, and Malassezia species-specific quantitative real-time polymerase chain reaction (qPCR) were performed. M. globosa was significantly more abundant on healthy canine skin by both methods (NGS P < .0001, qPCR P < .0001). M. restricta was significantly more abundant on healthy skin by NGS (P = .0023), and M. pachydermatis was significantly more abundant on naturally-affected allergic skin by NGS (P < .0001) and on allergen-induced atopic skin lesions by qPCR (P = .0015). Shifts in Malassezia populations were not observed in correlation with the development of allergen-induced skin lesions. Differences in the lipid dependency of predominant Malassezia commensals between groups suggests a role of the skin lipid content in driving community composition and raises questions of whether targeting skin lipids with therapeutics could promote healthy Malassezia populations on canine skin.

Critically appraised topic on adverse food reactions of companion animals (9): time to flare of cutaneous signs after a dietary challenge in dogs and cats with food allergies.

BACKGROUND: At this time, elimination diets followed by oral food challenges (OFCs) represent the "gold standard" for diagnosing skin-manifesting food allergies (FA) in dogs and cats. Regrettably, there is no clear consensus on how long one should wait for clinical signs to flare after an OFC before diagnosing or ruling-out a FA in a dog or a cat. RESULTS: We searched two databases on October 23, 2019 to look for specific information on the time for a flare of clinical signs to occur during OFCs after elimination diets in dogs and cats with skin-manifesting FAs. Altogether, we reviewed the study results of nine papers that included 234 dogs and four articles containing data from 83 cats. As multiple OFCs could be done in the same patient and not all animals included were subjected to an OFC, we were able to compile 315 and 72 times to flare (TTF) after an OFC in dogs and cats, respectively. When regrouping all cases together, about 9% of dogs and 27% of cats exhibited a flare of clinical signs in the first day after an OFC; 21% of dogs and 29% of cats had such relapse by the end of the second day. The time needed for 50 and 90% of dogs to exhibit a deterioration of clinical signs (TTF50 and TTF90) was 5 and 14, respectively; in cats, these times were 4 and 7 days, respectively. By 14 days after an OFC, nearly all food-allergic patients from both species had had a relapse of clinical signs. These results are limited by the likely under-reporting of flares that occur on the first day immediately following an OFC, the time in which IgE-mediated acute allergic reactions typically develop. CONCLUSION: Veterinary clinicians performing an OFC need to wait for 14 and 7 days for more than 90% of dogs and cats with a skin-manifesting FA to have a flare of clinical signs, respectively.