Comparison of selected cytomorphological features of canine pemphigus foliaceus and superficial pyoderma.

BACKGROUND: Cytological detection of acantholytic keratinocytes (acantholytic cells [AC]) helps to identify canine pemphigus foliaceus (cPF) yet AC also occurs in superficial pyoderma (SP), the main differential diagnosis. HYPOTHESIS/OBJECTIVES: To compare selected cytomorphological features of cPF and SP and to establish cytological diagnostic criteria that could differentiate cPF from SP. ANIMALS: 40 and 51 client-owned dogs with PF and SP, respectively. MATERIALS AND METHODS: Impression smears from cPF (64), impetigo (40) and exfoliative superficial pyoderma (ESP) (17) samples were stained with Romanowsky stain, randomised, blinded and evaluated by two investigators independently. The entire sample was screened (×500 or ×1000 magnification) for round (AC1), boat (AC2) and raft AC, eosinophils and bacteria. Interobserver agreements were calculated. RESULTS: The average number of the 10 highest ×500 fields for AC1 and AC2 was significantly higher in PF than SP (p < 0.0001; Kruskal-Wallis test). Rafts and eosinophils were more common in PF than SP (p < 0.0001; chi-square test), while bacteria were rare in PF (5%; p < 0.0001; chi-square test). Observations between the experienced and novice investigators were highly correlated. An ROC analysis identified five AC1/×500-magnification field as a suitable cut-off value for predicting PF diagnosis. This cut-off value was tested by two additional investigators, who identified sensitivity of 84%-100%, specificity of 95%-97% and accuracy of 95%-96% for the diagnosis of cPF. CONCLUSIONS AND CLINICAL RELEVANCE: Criterion-based impression smear cytological evaluation can provide strong evidence to support the clinical diagnosis. Acantholytic cell morphology varies in cPF and SP, and experience can improve accuracy in cytological differentiation.

Re-evaluating the prevalence of anti-desmocollin-1 IgA autoantibodies in canine pemphigus foliaceus.

Pemphigus foliaceus (PF) is an autoimmune skin disease of dogs characterized by intraepidermal pustules containing neutrophils and dissociated keratinocytes that develop in association with circulating and tissue-bound IgG autoantibodies. A subset of IgG autoantibodies in canine PF target desmocollin-1 (DSC1), a component of intercellular adhesion complexes within the epidermis. Passive transfer of IgG autoantibodies from canine PF sera to mice was previously shown to induce skin disease in the absence of infiltrating neutrophils. In attempts to identify a mechanism responsible for neutrophil recruitment, past studies evaluated the prevalence of IgA autoantibodies in canine PF sera where they were found in <20% of affected dogs. We re-evaluated the prevalence of anti-DSC1 IgA in canine PF due to concerns regarding the sensitivity of previously used methods. We hypothesized that anti-DSC1 IgA are present in most dogs with PF but have been under-detected due to competition with concurrent anti-DSC1 IgG for binding to their mutual antigenic target. Despite removing approximately 80% of IgG from patient sera using affinity chromatography, we did not detect an increase in anti-DSC1 IgA by performing indirect immunofluorescence on canine DSC1-transfected HEK293T cells. Taken together, our results do not support a role for pathogenic IgA in canine PF.

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.

Erosive and ulcerative stomatitis in dogs and cats: which immune-mediated diseases to consider?

Immune-mediated and autoimmune diseases of the skin often present with oral cavity involvement. Autoimmune subepidermal blistering diseases and pemphigus vulgaris are classic examples. While the primary lesions (vesicles and bullae) are relatively specific, these fragile lesions evolve rapidly into erosions and ulcers, which are lesion types that overlap with many diseases. Furthermore, some immune-mediated diseases such as severe adverse drug reactions, lupus diseases, canine uveodermatological syndrome, and vasculitis, may or may not involve the oral cavity, and often nonoral clinical manifestations are more diagnostic. In these situations, disease knowledge combined with signalment, lesion distribution, and history help to narrow the differentials. Surgical biopsy is required for confirmation in most diseases, while immunosuppressive treatments most typically involve glucocorticoids with or without nonsteroidal immunosuppressants.

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.

Long-term effects of ciclosporin and oclacitinib on mediators of tolerance, regulatory T-cells, IL-10 and TGF-ß, in dogs with atopic dermatitis.

BACKGROUND: Atopic dogs often are managed with allergen-specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T-cell (Treg) induction. HYPOTHESIS/OBJECTIVES: We evaluated Treg cell numbers and serum interleukin (IL)-10 and transforming growth factor-beta (TGF-ß)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months. ANIMALS: We included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate-to-severe AD and 15 atopic dogs controlled with AIT. MATERIALS AND METHODS: Peripheral blood CD4+CD25+FOXP3+ T-cell percentages were determined using flow cytometry. Serum concentrations of IL-10 and TGF-ß1 were measured by enzyme-linked immunosorbent assay. RESULTS: The percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p = 0.0003), the nontreated AD group (p = 0.0056) or the AIT group (p = 0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT-treated dogs. No significant differences were detected in IL-10 and TGF-ß1 serum concentrations between the five groups. CONCLUSIONS AND CLINICAL RELEVANCE: Lower Treg cell percentages in the CSA-treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance.

Trunk-dominant and classic facial pemphigus foliaceus in dogs - comparison of anti-desmocollin-1 and anti-desmoglein-1 autoantibodies and clinical presentations.

BACKGROUND: Canine trunk-dominant pemphigus foliaceus (PF) is mentioned rarely in the literature. HYPOTHESIS/OBJECTIVES: The goal of this study was to provide clinical description of trunk-dominant PF and to demonstrate the prevalence of serum antikeratinocyte, anti-desmocollin-1 (DSC1) and anti-desmoglein-1 (DSG1) antibodies, and determine their diagnostic value in this particular PF phenotype. MATERIALS AND METHODS: Clinically relevant information was collected from 31, 25 and 34 dogs with trunk-dominant and facial PF and superficial pyoderma (SP), respectively. Sera from these dogs were tested for antikeratinocyte, anti-DSC1 and anti-DSG1 antibodies using indirect immunofluorescence on canine tissues and DSC1- and DSG1-transfected cells. Sera from healthy dogs and dogs with clinically irrelevant diseases served as controls. RESULTS: Footpad involvement and grouped/polycyclic lesion organisation were identified as features of both PF phenotypes, and not of SP. Antikeratinocyte immunoglobulin (Ig)G was not specific for canine PF. By contrast, antigen-specific IgG was detected only in PF sera; anti-DSC1 IgG in 100% and 58% of dogs with facial and trunk-dominant PF, respectively, and anti-DSG1 IgG in 7% of dogs with trunk-dominant PF only. CONCLUSIONS: Trunk-dominant PF shares DSC1 as a major autoantigen with facial PF. The ability to detect anti-DSC1 IgG is lower in trunk-dominant PF, yet despite the lower sensitivity, the positive predictive value and accuracy of this particular anti-DSC1 IgG test are high. A negative test result, however, cannot exclude the diagnosis, and characteristic clinical features such as footpad involvement and/or grouped/polycyclic lesions must be considered when distinguishing trunk-dominant PF from its most relevant differential diagnosis: SP.

Contexte - Le pemphigus foliacé (PF) dominant le tronc chez le chien est rarement mentionné dans la littérature. Hypothèse/Objectifs - Le but de cette étude était de fournir une description clinique du PF dominant le tronc et de démontrer la prévalence des anticorps sériques anti-kératinocytes, anti-desmocolline-1 (DSC1) et anti-desmogléine-1 (DSG1), et de déterminer leur valeur diagnostique dans ce phénotype particulier de PF. Matériels et méthodes - Des informations cliniquement pertinentes ont été recueillies auprès de 31, 25 et 34 chiens atteints respectivement de PF à dominante tronculaire et faciale et de pyodermite superficielle (SP). Les sera de ces chiens ont été testés pour les anticorps anti-kératinocytes, anti-DSC1 et anti-DSG1 en utilisant l'immunofluorescence indirecte sur des tissus canins et des cellules transfectées avec DSC1 et DSG1. Des sera de chiens sains et de chiens atteints de maladies cliniquement non pertinentes ont servi de témoins. Résultats - L'implication du coussinet plantaire et l'organisation des lésions groupées / polycycliques ont été identifiées comme des caractéristiques des deux phénotypes PF, et non de SP. L'immunoglobuline antikératinocytaire (Ig)G n'était pas spécifique du PF canin. En revanche, l'IgG spécifique de l'antigène n'a été détectée que dans les sera de PF ; IgG anti-DSC1 chez 100 % et 58 % des chiens atteints de PF faciale et tronc-dominante, respectivement, et anti-DSG1 IgG chez 7 % des chiens avec PF tronc-dominant uniquement. Conclusions - Le PF à dominante tronculaire partage DSC1 comme auto-antigène majeur avec le PF facial. La capacité à détecter les IgG anti-DSC1 est plus faible chez les PF à dominante tronculaire, mais malgré la sensibilité plus faible, la valeur prédictive positive et la précision de ce test IgG anti-DSC1 particulier sont élevées. Cependant, un résultat de test négatif ne peut pas exclure le diagnostic, et les caractéristiques cliniques caractéristiques telles que l'atteinte du coussinet plantaire et/ou les lésions groupées/polycycliques doivent être prises en compte lors de la distinction entre la PF à dominante tronculaire et son diagnostic différentiel le plus pertinent : la SP.

Introducción- el pénfigo foliáceo (PF) de distribución truncal predominante se describe raramente n la literatura. Hipótesis/Objetivos- el objetivo de este estudio fue proporcionar una descripción clínica del PF truncal y demostrar la prevalencia de anticuerpos séricos antiqueratinocitos, antidesmocolina-1 (DSC1) y antidesmogleína-1 (DSG1), y determinar su valor diagnóstico en este fenotipo PF particular. Materiales y métodos- se recopiló información clínicamente relevante de 31, 25 y 34 perros con PF dominante truncal, PF dominante facial y pioderma superficial (PS), respectivamente. Los sueros de estos perros se analizaron en busca de anticuerpos antiqueratinocitos, anti-DSC1 y anti-DSG1 mediante inmunofluorescencia indirecta en tejidos caninos y células transfectadas con DSC1 y DSG1. Sueros de perros sanos y perros con enfermedades clínicamente irrelevantes sirvieron como controles. Resultados- la afectación de la almohadilla plantar y la organización de lesiones agrupadas/policíclicas se identificaron como características de ambos fenotipos de PF y no de SP. La inmunoglobulina (Ig)G antiqueratinocitos no fue específica para la PF canina. Por el contrario, la IgG específica de antígeno se detectó solo en sueros PF; IgG anti-DSC1 en el 100 % y el 58 % de los perros con PF predominante en la cara y el tronco, respectivamente, y IgG anti-DSG1 en el 7 % de los perros con PF predominante en el tronco solamente. Conclusiones- el PF dominante truncal comparte DSC1 como un autoantígeno importante con el PF facial. La capacidad para detectar IgG anti-DSC1 es menor en la PF dominante truncal; sin embargo, a pesar de la menor sensibilidad, el valor predictivo positivo y la precisión de esta prueba de IgG anti-DSC1 en particular son altos. Sin embargo, un resultado negativo de la prueba no puede excluir el diagnóstico, y deben tenerse en cuenta las características clínicas, como la afectación de las almohadillas plantares y/o las lesiones agrupadas/policíclicas, al distinguir la PF dominante truncal de su diagnóstico diferencial más relevante: SP.

Contexto - O pênfigo foliáceo (PF) canino predominante no tronco é raramente relatado na literatura. Hipótese/Objetivos - O objetivo deste estudo foi apresentar a descrição clínica do PF predominante no tronco e demonstrar a prevalência de anticorpos anti-queratinócitos, anti-desmocolina-1 (DSC1) e anti-desmogleína-1 (DSG1), e determinar o seu potencial diagnóstico neste tipo particular de PF. Materiais e métodos - Informações clinicamente relevantes foram coletadas de 31, 25 e 34 cães com PF predominante no tronco, PF facial e piodermite superficial (PS), respectivamente. Os soros destes cães foram testados para anticorpos anti-queratinócitos, anti-DSC1 e anti-DSG1 utilizando imunofluorescência indireta em tecidos caninos e em células DSC1 e DSG1 transfectadas. Os soros de cães saudáveis e cães com doenças clinicamente irrelevantes serviram de controle. Resultados - O acometimento dos coxins e a organização agrupada/policíclica das lesões foram identificadas como características de ambos os fenótipos de PF, não de PS. A imunoglobulina (Ig)G anti-queratinócitos não foi específica para PF. Em contraste, IgG antígeno-específica foi detectada apenas no soro de PF; IgG anti-DSC1 em 100% e 58% dos cães com PF facial e predominante no tronco, respectivamente, e IgG anti-DSG1 em 7% dos cães somente acometidos pelo PF predominante no tronco. Conclusões - O PF predominante no tronco compartilha DSC1 como um autoantígeno principal com PF facial. A capacidade de detectar IgG anti-DSC1 é menor no PF predominante no tronco, mas apesar da sensibilidade mais baixa, o valor preditivo positivo e a precisão do teste IgG anti-DSC1 específico são altos. Um resultado de teste negativo, no entanto, não pode excluir o diagnóstico, e características clínicas típicas, como envolvimento do coxim plantar e/ou lesões agrupadas/policíclicas, devem ser consideradas ao distinguir PF predominante no tronco de seu diagnóstico diferencial mais relevante: PS.

Comorbidity of ectopic thymoma-associated exfoliative dermatitis and pemphigus foliaceus in a cat.

An 8-year-old cat was presented with pruritus, purulent paronychia, scaling, crusting, and spontaneous alopecia. Histopathology revealed intraepidermal neutrophilic pustular acantholytic dermatitis and hyperkeratotic cytotoxic interface dermatitis. No thoracic mass was seen on a lateral radiograph. Ectopic thymoma was discovered on necropsy. This case highlights the necessity for thorough investigation of any case of feline exfoliative dermatitis and pemphigus foliaceus for the presence of thymoma. Key clinical message: Comorbidity of exfoliative dermatitis and pemphigus foliaceus in a cat should prompt a thorough investigation for presence of a thymoma, possibly with advanced imaging techniques.

Comorbidité de dermatite exfoliative et de pemphigus foliacé associés à un thymome ectopique chez un chat. Un chat de 8 ans a été présenté avec prurit, panaris purulent, desquamation, croûtes et alopécie spontanée. L'histopathologie a révélé une dermatite acantholytique neutrophilique intra-épidermique et une dermatite d'interface cytotoxique hyperkératosique. Aucune masse thoracique n'a été observée sur une radiographie latérale. Un thymome ectopique a été découvert à l'autopsie. Ce cas met en évidence la nécessité d'une investigation approfondie de tout cas de dermatite exfoliative féline et de pemphigus foliacé pour la présence d'un thymome.Message clinique clé :La comorbidité d'une dermatite exfoliative et de pemphigus foliacé chez un chat devrait inciter à une enquête approfondie pour la présence d'un thymome, éventuellement avec des techniques d'imagerie avancées.(Traduit par Dr Serge Messier).

Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement.

BACKGROUND: Junctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone. OBJECTIVES: To characterize the clinical and morphological features of a congenital mechanobullous disease in a litter of puppies with severe upper respiratory involvement, and to identify an associated genetic variant. ANIMALS: Five of eight puppies in an Australian cattle dog cross-bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress. Additionally, one unaffected sibling was examined and blood was obtained for genetic testing. METHODS AND MATERIALS: Post-mortem examination, histopathological evaluation and electron microscopy were performed. Whole genome sequencing (WGS) of one affected puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant. RESULTS: Clinically, severe mucocutaneous ulcers occurred in frictional areas with claw sloughing. Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post-mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway. Moderate tracheal hypoplasia contributed. The WGS revealed a novel missense variant in the laminin α3-chain XP_537297.2p(Asp2867Val), with an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: A novel variant in LAMA3 caused a generalized and severe phenotype of JEB with an unique clinical presentation of upper airway obstruction.

Bullous amyloidosis in a horse: first description in veterinary medicine.

BACKGROUND: Bullous amyloidosis is a rare disease in humans that has not been described in a veterinary species in the peer-reviewed literature. The human disease is characterised by haemorrhagic vesicles and bullae on the skin and mucosae, which form due to amyloid deposition. HYPOTHESIS/OBJECTIVES: To describe the clinical features, laboratory analysis and histopathological features of an unique presentation of bullous disease in a horse. ANIMALS: A 17-year-old thoroughbred mare presented for weight loss and severe oral cavity ulcers. METHODS AND MATERIALS: Investigations involved haematological evaluation, chemistry profiles, gastroscopy and serum protein electrophoresis, and, postmortem, histopathological evaluation, Congo-red staining and transmission electron microscopy (TEM). RESULTS: Haemorrhagic vesicles and bullae occurred on the mucosa of the oral cavity, lips, oesophagus and stomach, and much less the muzzle, face and mucocutaneous areas of the perineum, where scarring was evident. Histopathological evaluation and Congo-red staining confirmed the presence of amyloid deposits in dermis and submucosa, in association with vesicle and bulla formation, consistent with bullous amyloidosis. TEM confirmed amyloid fibril deposition in the dermis and along the basement membrane zone. Clefts occurred in the superficial dermis and submucosa, which explained haemorrhage and scarring. The presence of a polyclonal gammopathy and the rapid abolishment of Congo-red staining with performate pretreatment supported serum amyloid A and secondary amyloidosis. CONCLUSION AND CLINICAL IMPORTANCE: Bullous amyloidosis is a novel disease of the horse and a newly recognised differential for bullous disease, for which the haemorrhagic nature of bullae, scarring and deep secondary ulcers are considered clinical clues to the condition.

Treatment of the feline atopic syndrome - a systematic review.

BACKGROUND: Feline allergic skin disease and asthma occur regularly in small animal practice. OBJECTIVES: To provide evidence-based recommendations for small animal practitioners on the treatment of feline atopic syndrome (FAS). METHODS AND MATERIALS: The authors reviewed the literature available before February 2020, prepared a detailed evidence-based literature review and made recommendations based on the evaluated evidence. RESULTS: Sixty-six papers and abstracts were identified describing treatment interventions for FAS and evaluated to establish treatment recommendations. For many treatment options, the papers were retrospective, open studies or case reports. CONCLUSION AND CLINICAL RELEVANCE: In this review, there was good evidence for the efficacy of systemic glucocorticoids and ciclosporin, and limited evidence for the efficacy of topical glucocorticoids, oclacitinib and allergen-specific immunotherapy in feline atopic skin syndrome. Evidence pointed to low-to-moderate efficacy for antihistamines, fatty acids and palmitoyl ethanolamide. In feline asthma, there was good evidence for the efficacy of oral and inhaled glucocorticoids, and limited evidence of moderate efficacy for allergen-specific immunotherapy. Evidence supported low-to-moderate efficacy of mesenchymal stem cells, inhaled lidocaine and oclacitinib as treatments for feline asthma. For almost all therapeutic options (with the exception of glucocorticoids and ciclosporin), more randomised controlled trials are needed.

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.

Open trial of Bruton's tyrosine kinase inhibitor (PRN1008) in the treatment of canine pemphigus foliaceus.

BACKGROUND: Bruton's tyrosine kinase (BTK) is important in B-cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is one of the most common canine autoimmune skin diseases. OBJECTIVES: To determine the safety and efficacy of the BTKi PRN1008 in the treatment of cPF. ANIMALS: Four privately owned dogs. METHODS AND MATERIALS: Four dogs diagnosed with PF were administered BTKi PRN1008. Initial dosages approximated to 15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for 20 weeks, attempting to decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels and urinalyses, and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Serum anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin (Ig)G titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells (PBMC). RESULTS: All four dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. Three dogs continued to improve and sustained near complete remission by 20 weeks, at which point three responses were considered "good" and one "fair". Final daily dosages were in the range 17-33 mg/kg. Anti-DSC-1 IgG titre decreased dramatically in one dog, was undetectable in two and was uninterpretable in one dog. No dogs had detectable IgG to DSG1. A possible adverse event occurred in one dog. CONCLUSIONS AND CLINICAL IMPORTANCE: BTKi PRN1008 monotherapy may have some beneficial effects in some cases of cPF.

Detection of circulating anti-keratinocyte autoantibodies in feline pemphigus foliaceus.

BACKGROUND: Circulating anti-keratinocyte immunoglobulin (Ig)G targeting desmosomal proteins have been identified in people and dogs with pemphigus foliaceus (PF). By contrast, detection attempts in PF-affected cats have been largely unsuccessful. HYPOTHESIS/OBJECTIVES: To detect circulating anti-keratinocyte autoantibodies in PF-affected cats and determine their titres and tissue-staining patterns. ANIMALS: Thirty PF-affected cats were compared to 11 specific-pathogen free, 15 healthy and 31 allergic cats. METHODS AND MATERIALS: Sera were tested by indirect immunofluorescence on canine footpad and buccal mucosal substrates. RESULTS: Circulating, anti-keratinocyte IgG with a suprabasilar, web-like (intercellular) pattern were detected in the majority of PF-affected cats (23 of 30, 77%), some allergic cats (six of 31, 19%) and one healthy cat (7%). Both footpad epidermis and buccal mucosa were positive in the majority of seropositive PF-affected cats (21 of 23, 91%), and in only one of six (17%) seropositive allergic cats. Staining was limited to the footpad in the remaining seropositive PF-affected and allergic cats and one seropositive healthy cat. Reciprocal IgG titres were significantly higher in PF-affected cats compared to controls (Dunn's post-test, P < 0.0001). Anti-keratinocyte IgM, IgA or IgE were not detected in any sera. CONCLUSIONS AND CLINICAL IMPORTANCE: These results confirm the presence of circulating anti-keratinocyte IgG in a majority of PF-affected cats and in a small percentage of healthy and allergic cats. Although the molecular target and pathogenic nature of the antibodies remains unknown, the detection of positive immunostaining on buccal mucosal tissue, in addition to the footpad, suggests that the major target antigen of feline PF differs from that reported in dogs.

Cutaneous polyautoimmunity in two unrelated dogs: pemphigus foliaceus and generalized discoid lupus erythematosus.

BACKGROUND: Polyautoimmunity, the concurrent expression of two or more distinct autoimmune diseases (ADs) in a single individual, is a known phenomenon in humans and has been rarely reported in dogs. To the best of the authors' knowledge, comorbid pemphigus foliaceus (PF) and generalized discoid lupus erythematosus (GDLE) has not been reported in dogs. HYPOTHESIS/OBJECTIVES: To describe the clinical, histological and immunological features and treatment outcome of two unrelated dogs with comorbid PF and GDLE. ANIMALS: One 10-year-old, spayed German shepherd dog and one 8-year-old, castrated American Staffordshire terrier presented for evaluation of a symmetrical, facial- and/or pedal-dominant pustular dermatitis with concurrent, truncal scaly plaques. METHODS: For each dog, clinicopathological characterization included physical examination, lesion cytological evaluation, bacterial culture and sensitivity testing, skin histopathological investigation and direct and indirect immunofluorescence testing. Additional diagnostic imaging and haematological testing was performed to exclude extracutaneous disease. RESULTS: Both dogs exhibited lesions clinically and histologically compatible with PF and GDLE. Moreover, one dog exhibited generalized leucotrichia and chronic superficial keratitis. Remission was achieved with immunosuppressive dosages of prednisolone [high-dose pulse (Case 1) or standard immunosuppressive dosage (Case 2)] and ciclosporin (5-6 mg/kg/day). Tissue-bound antikeratinocyte immunoglobulin (Ig)G and IgM were detected in both dogs. A weak basement membrane zone deposit of C3 was seen in one dog. Circulating antikeratinocyte and anti-desmocollin-1 IgG were detected in one dog. CONCLUSIONS AND CLINICAL IMPORTANCE: Cutaneous polyautoimmunity can occur in the dog. Depending on the specific disease combinations, overlapping clinical features may present diagnostic and/or therapeutic challenges. Moreover, these cases should be monitored for development of additional cutaneous or extra-cutaneous AD(s).

Rapid response of hyperkeratotic erythema multiforme to oclacitinib in two dogs.

BACKGROUND: Hyperkeratotic erythema multiforme (HKEM) is a clinically distinct dermatosis and poorly characterized syndrome, comprised of hyperkeratotic plaques with variable symmetry and apoptosis similar to "classic" erosive canine EM. Hyperkeratotic EM has a protracted clinical course and, although treatments with glucocorticoids, azathioprine and/or ciclosporin have been tried, rates of remission are low. OBJECTIVES: To describe successful treatment of HKEM in two dogs using oclacitinib. ANIMALS: A 7-year-old, spayed Havanese dog (Case 1) and a 1-year-old, intact cryptorchid Dachshund dog (Case 2). METHODS: Case characterization and clinical diagnoses were based on lesion character, surgical biopsy, cytological evaluation, culture, direct immunofluorescence (DIF) and expected responses to treatments. RESULTS: Both cases exhibited multifocal, often symmetrical hyperkeratotic plaques with adherent scale. Histological findings revealed prominent epidermal hyperplasia, parakeratotic hyperkeratosis, lymphocytic dermatitis and transepidermal apoptosis with lymphocytic satellitosis. DIF revealed fine, patchy IgG, IgM and IgA basement membrane deposits (Case 2). Both dogs exhibited rapid improvement with oral oclacitinib (0.6-0.9 mg/kg twice daily) with a complete remission of clinical signs observed in 12 and seven weeks in cases 1 and 2, respectively. CONCLUSION AND CLINICAL IMPORTANCE: Oclacitinib could be considered as a fast-acting and effective treatment option for HKEM in dogs.

Detection of circulating anti-retinal antibodies in dogs with sudden acquired retinal degeneration syndrome using indirect immunofluorescence: A case-control study.

Sudden acquired retinal degeneration syndrome (SARDS) in dogs is proposed to have an immune-mediated etiology. However, there is conflicting evidence regarding the presence of antiretinal antibodies, as assessed by western blotting, in the serum of SARDS patients. Because of the possibility that antibodies recognize only conformational epitopes, we hypothesized that a more sensitive method to investigate circulating retinal autoantibodies in SARDS is immunofluorescence. Sera from 14 dogs with early SARDS, and 14 age- and breed-matched healthy control dogs were screened for circulating antiretinal IgG, IgM, IgE and IgA using indirect immunofluorescence on lightly fixed frozen sections of normal canine retina. Controls without canine serum were also performed. A nuclear counterstain was used to identify cellular retinal layers. Images were obtained using a fluorescence microscope, and 2-3 separate masked observers graded retinal layers for fluorescence staining intensity using a 0-3 scale. Total circulating IgG and IgM was assessed by radial immunodiffusion. Statistical analysis was performed using 2-way ANOVA, paired 2-tailed student's t-test and correlation analysis. Intensity of IgG staining of photoreceptor outer segments was significantly higher using serum from dogs with SARDS compared with healthy controls in 2/3 observers (P < 0.05). Intensity of IgM staining throughout the retina was higher in SARDS dogs compared to matched healthy controls (P < 0.0001), although no specific retinal layer was statistically significant. There were no differences in staining intensity for IgE or IgA. Dogs with SARDS had a comparably lower circulating IgG and higher IgM than healthy controls (P = 0.01 and 0.001 respectively) and IgG and IgM were negatively correlated (r = -0.69, P = 0.007). Despite having decreased serum IgG compared with healthy controls, circulating IgG in dogs with SARDS binds photoreceptor outer segments to a greater extent. Dogs with SARDS have a relatively higher circulating IgM than matched healthy controls. The pathogenic nature of these antibodies is unknown.

Efficacy of a Bruton's Tyrosine Kinase Inhibitor (PRN-473) in the treatment of canine pemphigus foliaceus.

BACKGROUND: Bruton's tyrosine kinase (BTK) is important in B-cell signalling. Efficacy has been reported for BTK inhibitors (BTKi) in human autoimmune diseases. Canine pemphigus foliaceus (cPF) is the most common canine autoimmune skin disease. OBJECTIVES: To determine the safety and efficacy of a BTKi in cPF treatment. ANIMALS: Nine privately owned dogs. METHODS AND MATERIALS: Nine dogs diagnosed with PF were administered BTKi PRN473. Initial dosages were ≈15 mg/kg once daily, increased to twice daily if inadequate response was seen. Treatment continued for a maximum of 20 weeks, attempting decrease to every other day. Dogs were monitored with complete blood counts, serum biochemistry panels, urinalyses and evaluated with a modified version of a validated human Pemphigus Disease Activity Index (cPDAI). Anti-desmocollin-1 (DSC-1) and desmoglein-1 (DSG-1) immunoglobulin G (IgG) titres were performed before and after the treatment period. Drug bound to target was measured in peripheral blood mononuclear cells. RESULTS: All nine dogs showed reduction in lesions and cPDAI score during the first two weeks of treatment. At the end of the study, four responses were considered "good", two "fair", two "poor" and one dog withdrawn due to recurrence of a previously excised mast cell tumour. Four dogs continued to improve by Week 4; three sustained near complete remission by study's end. The anti-DSC-1 IgG titre decreased in three dogs, increased in two, was undetected in three and was not performed in the withdrawn dog. No dogs had detectable IgG to DSG1. Possible adverse effects occurred in three dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Bruton's tyrosine kinase inhibitor monotherapy may have beneficial effects in some cases of cPF.

The usefulness of short-course prednisolone during the initial phase of an elimination diet trial in dogs with food-induced atopic dermatitis.

BACKGROUND: Food allergy is a possible cause of atopic dermatitis (AD) in dogs; it is typically diagnosed following an eight-week elimination diet trial (EDT) and a provocation with the original diet. This lengthy procedure is difficult for owners and its interpretation may be unclear. HYPOTHESIS/OBJECTIVES: To test the effect of prednisolone used in the first weeks of an EDT in order to reduce the total time period for diagnosis. The goal was to perform food challenges earlier than after the traditionally recommended eight weeks. ANIMALS: Fifty-three dogs with AD were included in the study. METHODS AND MATERIALS: All dogs were fed a commercially available extensively hydrolyzed protein-based commercial pet food and treated with prednisolone for at least two weeks to control pruritus and inflammation. Dogs were challenged two weeks after prednisolone finished, provided that no flare had occurred. Dogs with relapsing signs were fed the hydrolyzate for at least eight weeks with or without further prednisolone treatment. RESULTS: Ten of 53 dogs (19%) had no relapse after two weeks off prednisolone: they were subsequently challenged with their regular food, had a relapse of signs and were diagnosed with a food-induced AD within four to six weeks of starting the EDT. In the other dogs, signs remained uncontrolled without prednisolone or relapsed rapidly after its discontinuation: they were considered nonfood-allergic after an eight week EDT. CONCLUSION AND CLINICAL IMPORTANCE: This study demonstrates that a shorter EDT is possible if the allergic pruritus and inflammation are initially controlled with a short course of glucocorticoids. This shortened trial is likely to improve owner adherence and facilitate the diagnosis of food allergy.