Efficacy of therapeutic plasma exchange in a case of severe, generalised canine pemphigus foliaceus.

Successful treatment of pemphigus foliaceus (PF) often requires a multimodal therapeutic approach. The dog described herein underwent four therapeutic plasma exchange treatments for severe, refractory PF, resulting in a 50% reduction of lesional body surface area. This treatment option should be considered for the management of canine PF.

O tratamento bem-sucedido do pênfigo foliáceo (PF) geralmente requer uma abordagem terapêutica multimodal. O cão aqui descrito foi submetido a quatro tratamentos de troca de plasma terapêutica (TPE) para PF grave e refratário, resultando em uma redução de 50% da área corpórea lesional. Esta opção de tratamento deve ser considerada para o manejo do PF canino.

El tratamiento exitoso del pénfigo foliáceo (PF) a menudo requiere un enfoque terapéutico multimodal. El perro aquí descrito se sometió a cuatro tratamientos terapéuticos de intercambio plasmático (TPE) para un PF refractario grave, lo que resultó en una reducción del 50% de la superficie corporal lesionada. Esta opción de tratamiento debe considerarse para el control de PF canino.

Traiter efficacement le pemphigus foliacé (PF) nécessite souvent une approche thérapeutique multimodale. Dans ce rapport clinique, un chie a reçu quatre traitements de plasmaphérèse thérapeutique (EPT) pour le traitement d'un PF sévère et réfractaire, ce qui a permis de réduire de 50 % la surface corporelle lésionnelle. Cette option thérapeutique devrait être envisagée pour la prise en charge du PF canin.

The use of oclacitinib compared to azathioprine in the management of canine pemphigus foliaceus: A retrospective analysis.

BACKGROUND: Oclacitinib (Apoquel; Zoetis) has been reported to be beneficial for treating immune-mediated disorders. HYPOTHESIS/OBJECTIVES: This retrospective study evaluates in which group of dogs [oclacitinib (OC) or azathioprine (AZ)] remission of pemphigus foliaceus (PF) was more effectively achieved with matched induction dosing of glucocorticoids; it further evaluates which group had a higher glucocorticoid-sparing effect. ANIMALS: Review of 30 medical records of dogs diagnosed with PF presented to a private practice dermatological service. MATERIALS AND METHODS: Retrospective analysis of dogs diagnosed with PF and treated with OC or AZ in combination with glucocorticoids. RESULTS: There was no significant difference in the ability to induce remission between AZ and OC groups. In the AZ group, 13 of 15 dogs went into some type of remission (partial or complete), compared with 11 of 15 in the OC group. There was no significant difference between the two groups for the glucocorticoid-sparing effect. The AZ group had an average reduction of 77.9% from the induction glucocorticoid dose, and OC group had an average reduction of 64.4%. One of 15 patients in the AZ group and three of 15 patients in the OC group had a 100% reduction of the glucocorticoid dose. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that OC can be considered as a treatment option for canine PF.

Characterization of the serum and skin inflammatory profile in canine pemphigus foliaceus using multiplex assay and quantitative real-time polymerase chain reaction (qRT-PCR).

Canine pemphigus foliaceus (PF) is a common autoimmune skin disease characterized by autoantibodies binding to epithelial adhesion molecules resulting inflammatory response. The immune network of cytokine and chemokine abnormalities that characterize the immune response in canine PF are poorly explored. This study evaluated serum and lesional skin cytokine and chemokine profiles of dogs diagnosed with PF compared to healthy control dogs. Serum samples obtained from 11 PF dogs and 16 healthy control dogs were analyzed using commercially available canine multiplex assay for 13 biomarkers (Canine Milliplex assay). Eight lesional skin samples from seven PF dogs and five healthy site-matched samples from five healthy dogs were evaluated for 20 immune markers using quantitative real-time PCR. Immunomodulating medications were suspended for at least four weeks in all dogs before obtaining serum and skin samples. PF patients showed significantly higher serum concentrations of tumor necrosis factor-α, interleukin (IL)- 6, IL-8, IL-18, CCL2, KC-like, and granulocyte-macrophages colony-stimulating factor when compared to healthy controls (Mann-Whitney U test; p < 0.05 for all). Lesional PF skin exhibited significant expression and upregulation of pro-inflammatory/T helper (Th1) 1 markers IL-1ß, MX1, GZMB, OAS1, and IFN-γ as well as Th2 cytokines IL-13, IL-33, TSLP, IL-31 and Th17/22 markers IL-17A and IL-22 (Mann-Whitney U test; p < 0.05 for all). Taken together, the findings from this study describe the role of numerous cytokines and chemokines associated with immune response in the skin and serum of canine PF patients. Further larger-sample proteomics and RNA-sequencing transcriptomics studies are needed to understand the immune pathogenesis of canine PF skin lesions.

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.

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.

Successful management of feline pemphigus foliaceus with pentoxifylline and topical hydrocortisone aceponate.

The treatment regimen for feline pemphigus foliaceus (PF), an autoimmune disease caused by auto-antibodies against proteins of the desmosome junction, usually includes high doses of oral or parenteral immunosuppressive drugs, typically glucocorticoids. This case adds to a growing body of evidence that topical hydrocortisone aceponate is effective for the treatment of feline PF, and demonstrates the practical use of a non-invasive diagnostic method for histopathology when owners refuse a biopsy to support a clinical diagnosis of PF. Finally, this case highlights an international trend of owner-initiated treatment of feline infectious peritonitis (FIP) using unlicensed, unregistered drugs.

A case report of the beneficial effect of oclacitinib in a dog with pemphigus vulgaris.

Pemphigus vulgaris is a rare immune-mediated skin disorder of the dog, usually treated with immunosuppressive medications such as oral glucocorticoids, azathioprine or ciclosporin. Herein we report the successful treatment of pemphigus vulgaris in a dog, using oclacitinib and a topical product containing fucidic acid (0.5 % w/w) and betamethasone valerate.

Le pemphigus vulgaire est une affection cutanée rare à médiation immune chez le chien, généralement traitée avec des médicaments immunosuppresseurs tels que les glucocorticoïdes oraux, l'azathioprine ou la ciclosporine. Nous décrivons ici le traitement efficace du pemphigus vulgaire chez un chien, à l'aide d'oclacitinib et d'un produit topique contenant de l'acide fucidique (0,5 % p/p) et du valérate de bétaméthasone.

O pênfigo vulgar é uma dermatopatia imunomediada dos cães, que é usualmente tratada com medicações imunossupressoras como corticoides por via oral, azatioprina ou ciclosporina. No presente estudo, relatamos o tratamento de bem sucedido de penfigp vulgaris em um cão, utilizando o oclacitinib e um produto tópico contendo ácido fusídico (0,5 % w/w) e valerato de betametasona.

El pénfigo vulgar es un trastorno inmunomediado cutáneo poco frecuente en perros, generalmente tratado con medicamentos inmunosupresores como glucocorticoides orales, azatioprina o ciclosporina. En este artículo describimos el tratamiento exitoso de pénfigo vulgar en un perro utilizando oclacitinib y un producto tópico que contiene ácido fucídico (0,5 % p/p) y valerato de betametasona.

A retrospective evaluation of the steroid sparing effects of oral mycophenolate mofetil (MMF) as an adjunct immunosuppressant for the treatment of canine pemphigus foliaceus.

BACKGROUND: Oral mycophenolate mofetil (MMF) currently is considered a low-risk steroid-sparing therapeutic option for the management of canine pemphigus foliaceus (PF). OBJECTIVES: This retrospective study evaluates the therapeutic outcomes of dogs with PF treated with the combination of oral MMF and glucocorticoid (GC). Clinical outcomes and adverse side effects are reported. ANIMALS: Eleven dogs diagnosed with PF. MATERIALS AND METHODS: Retrospective review of medical records from dogs presented with PF to the dermatology service of a veterinary teaching hospital between 2015 and 2020. RESULTS: Eleven dogs were identified which had received concurrent GCs and MMF. The MMF dose range was 19.8-45 mg/kg/day. Only two dogs (two of 11) treated with a mean MMF dosage of 39 mg/kg/day along with oral prednisone or dexamethasone achieved complete remission (CR). Partial remission (PR) was achieved in four of 11 dogs who received either prednisone, prednisolone or dexamethasone along with MMF (mean dosage 26 mg/kg/day). Four dogs (four of 11) showed poor response to MMF given at 28.5 mg/kg/day along with prednisone or dexamethasone. In one dog (one of 11) MMF was discontinued due to severe GI upset; transient vomiting and diarrhea was observed in four of 11 dogs. The median duration of MMF therapy in conjunction with GC for all groups was 70.5 days. Tapering of oral GCs while continuing MMF administration at the same dosage and frequency led to recurrence of lesions in all PF patients. CONCLUSION: Oral MMF combined with GC achieved CR in two of 11 PF dogs included in this study. Further research of MMF efficacy in PF may need to be performed.

Skin disease in goats (Capra aegagrus hircus): a retrospective study of 358 cases at a university veterinary teaching hospital (1988-2020).

BACKGROUND: Goats are important worldwide as a source of milk, meat, fibre and hide, and as show animals and pets. HYPOTHESIS/OBJECTIVES: To document the type, signalment associations and prevalence of skin disease in a referral hospital population. ANIMALS: Case population at a university veterinary teaching hospital. METHODS AND MATERIALS: Retrospective study by searching computerised medical records of goats seen between 1 January 1988 and 1 January 2021. Key words employed were "alopecia, caseous lymphadenitis, Chorioptes, dermatitis, dermatophyte, dermatophytosis, goat, lice, louse, mange, mite, pemphigus foliaceus, Psoroptes, ringworm, seborrhea, skin" RESULTS: Of 1,488 records reviewed, 358 (24%) goats had skin disease recorded. Seventy-nine (22.1%) of 358 goats presented primarily for skin disease. The Nigerian Dwarf goat breed was at higher risk of developing skin disease (P < 0.0002). As goats aged, the odds for developing skin disease was higher [odds ratio (OR) = 1.07 per year, 95% confidence interval (1.04, 1.12)] as was the predilection for malignant skin tumours (P < 0.001). Sex was not associated with skin disease (P = 0.98). The most common clinical sign was exfoliative dermatitis, noted in 94 (26.4%) of 358 goats. The most common diagnoses were pediculosis, bacterial skin disease and squamous cell carcinoma. Less frequent diagnoses were Chorioptes spp. infestation, contagious ecthyma (orf), coronitis/interdigital dermatitis, demodicosis, dermatophytosis, Psoroptes spp. infestation, dermatophilosis and pemphigus foliaceus. CONCLUSIONS AND CLINICAL IMPORTANCE: Skin diseases are common in goats. Nigerian Dwarf goats and older goats are at greater risk of developing skin disease; Nigerian Dwarf goats had a predilection for malignant skin tumours. Clinicians should include a dermatological examination in goats regardless of the reason for presentation.

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).

State-of-the-art review of human autoimmune blistering diseases (AIBD).

Autoimmune blistering diseases (AIBDs) are a heterogenous group of skin conditions, broadly classified into two categories depending on the location of blister formation: intraepidermal blistering in the pemphigus group and subepidermal blistering in the pemphigoid group. Although AIBDs occur in both humans and animals, the arsenal of data for human AIBDs far exceeds those of their animal counterpart. Therefore, the main purpose of this review is to highlight existing knowledge, and recent advances in the diagnosis and management of AIBDs in humans - to serve as a road map for veterinary dermatologists. AREAS COVERED: Recent findings include complement-independent pathways in the pathogenesis of bullous pemphigoid, as well as the role of desmoglein and desmocollin autoantibodies in inducing acantholysis. Systemic glucocorticoids are the mainstay of treatment for AIBDs in humans, yet their long-term use is associated with severe adverse effects and complications, thereby limiting their use. Therefore, researchers have been exploring new and safer alternative therapeutic options for human AIBDs such as anti-CD20 monoclonal antibodies (Rituximab), Bruton's tyrosine kinase inhibitors (BTKi) and neonatal Fc receptor (FcRn) blockers. EXPERT OPINION: Randomised controlled trial (RCT) level evidence show that Rituximab and short-course GC regimes are more effective and safer than traditional GC treatment for human AIBDs. FcRn blockers such as SYNT001 have shown positive results in preliminary phase 2 clinical trials for treatment of human pemphigus; further trials are required. Rilzabrutinib (PRN1008), an orally administered BTKi, has recently completed phase 2 trials in pemphigus and is in a phase 3 RCT in humans.

Les maladies auto-immunes de clivage (AIBDs) est un groupe hétérogène de maladies cutanées, classifiées en deux catégories dépendantes de la localisation du clivage : intra-épidermique dans le groupe pemphigus et sous-épidermique dans le groupe pemphigoïde. Bien que les AIBDs existent chez l'homme et chez l'animal, l'arsenal de données pour les AIBDs de l'homme est bine plus développé que pour l'animal. Ainsi, le principal objectif de cette revue et de mettre en lumière les connaissances existantes et les avancées récentes du diagnostic et de la gestions des AIBDs de l'homme- afin de servir de carte de route pour les vétérinaires dermatologues. ZONES COUVERTES: Des données récentes comprennent les voies indépendantes du complément dans la pathogénie de la pemphigoïde bulleuse, ainsi que le rôle de la desmogléine et desmocolline dans la formation de l'acantholyse. Les corticoïdes (GC) systémiques sont le principal traitement des AIBDs de l'homme, bien que leur utilisation au long court avec effets secondaires sévères et complications, limitent leur utilisation. Ainsi, les chercheurs ont explorés de nouvelles options thérapeutiques alternatives plus sures pour les AIBDs de l'homme tels que les anticorps monoclonaux anti-CD20 (Ritumimab), les inhibiteurs de tyrosine kinase de Bruton (BTKi) et des bloqueurs de récepteur Fc néonataux (FcRn). POSITION DES EXPERTS: Les niveaux de preuves des essais contrôlés randomisés (RCT) montrent que le Ritumimab et les traitements de corticoïdes de courte durée sont plus efficaces et plus surs que les traitements traditionnels de GC pour les AIBDs de l'homme. Les bloqueurs FcRn tels que SYNT001 ont montré des résultats positifs dans les essais préliminaires cliniques de phase 2 pour le traitement du pemphigus de l'homme ; d'autres études sont nécessaires. Le Rilzabrutinib (PRN1008), un BTKi oral, a récemment fini un essai de phase 2 dans le pemphigus et une étude de phase 3 RCT chez l'homme.

Las enfermedades autoinmunes ampulosas (AIBDs, por sus siglas en inglés) son un grupo heterogéneo de afecciones cutáneas, que se clasifican ampliamente en dos categorías según la ubicación de la formación de ampollas: ampollas intraepidérmicas en el grupo de pénfigo y ampollas subepidérmicas en el grupo de penfigoides. Aunque los AIBD ocurren tanto en humanos como en animales, el arsenal de datos para los AIBD humanos supera con creces a los de sus homólogos animales. Por lo tanto, el propósito principal de esta revisión es resaltar el conocimiento existente y los avances recientes en el diagnóstico y manejo de los AIBD en humanos, para que sirva como una hoja de ruta para los dermatólogos veterinarios. ÁREAS CUBIERTAS: los hallazgos recientes incluyen vías independientes del complemento en la patogenia del penfigoide ampuloso, así como el papel de los autoanticuerpos de desmogleína y desmocolina en la inducción de acantólisis. Los glucocorticoides sistémicos son el pilar del tratamiento para los AIBD en humanos, sin embargo, su uso a largo plazo se asocia con efectos adversos graves y complicaciones, lo que limita su uso. Por lo tanto, los investigadores han estado explorando opciones terapéuticas alternativas nuevas y más seguras para las AIBDs humanas, como los anticuerpos monoclonales anti-CD20 (Rituximab), los inhibidores de la tirosina quinasa de Bruton (BTKi) y los bloqueadores del receptor de Fc neonatal (FcRn). OPINIÓN DE EXPERTOS: la evidencia a nivel de ensayos controlados aleatorios (RCT) muestra que los regímenes de Rituximab y GC de ciclo corto son más efectivos y más seguros que el tratamiento GC tradicional para los AIBD humanos. Los bloqueadores de FcRn como SYNT001 han mostrado resultados positivos en ensayos clínicos preliminares de fase 2 para el tratamiento del pénfigo humano; se requieren más pruebas. Rilzabrutinib (PRN1008), un BTKi administrado por vía oral, ha completado recientemente ensayos de fase 2 en pénfigo y se encuentra en un RCT de fase 3 en humanos.

As doenças autoimunes bolhosas (DAIBs) são um grupo heterógeno de dermatopatias, amplamente classificadas em duas categorias, dependendo da localização da formação das bolhas: bolhas intraepidermais no grupo do pênfigo e bolhas subepidermais no grupo penfigoide. Apesar das DAIBs ocorrerem tanto nos humanos quanto nos animais, o arsenal de dados sobre as DAIBs humanas é muito maior que o existente para animais. Desta forma, o principal propósito desta revisão é destacar o conhecimento existente, e os recentes avanços no diagnóstico e manejo das DAIBs em humanos - para servir como um roteiro para os dermatologistas veterinários. ÁREAS ABORDADAS: Os achados recentes incluem vias independentes do complemento na patogênese do penfigoide bolhoso, bem como a função dos autoanticorpos anti-desmogleína e anti-desmocolina induzindo acantólise. Glicocorticoides sistêmicos são a base do tratamento das DAIBs em humanos, apesar de seu uso prolongado ser associado a reações adversas e complicações graves,9R limitando assim o seu uso. Desta forma, os pesquisadores têm explorado novas alternativas terapêuticas mais seguras para as DAIBs humanas, tais como os anticorpos monoclonais anti-CD20 (Rituximab), inibidores de tirosina quinase de Bruton (BRKi) e bloqueadores de receptores Fc neonatais (FcRn). OPINIÃO DO ESPECIALISTA: Evidências de ensaios clínicos randomizados e controlados (RCT) demonstram que o Rituximab e terapias de curta duração com GC são mais eficazes e seguros que a terapia tradicional com GC para DAIBs humanas. Os bloqueadores de FcRn, como SYNT001, demostraram resultados positivos em ensaios clínicos preliminares de fase 2 para o tratamento de pênfigo humano; mais ensaios são necessários. Ensaios de fase 2 em pênfigo com o Rilzabrutinib (PRN1008), um BTKi administrado por via oral, foram concluídos e estão conduzindo os ensaios RCT de fase 3 em humanos.

Pemphigus foliaceus in Arabian oryx (Oryx leucoryx).

Pemphigus foliaceus (PF) is an autoimmune acantholytic skin disease described in humans, dogs, cats, horses, goats, and sheep. From 2003 to 2016, six Arabian oryx (Oryx leucoryx) at the National Zoological Garden in Pretoria, South Africa, developed progressive, bilaterally symmetrical, hyperkeratotic skin lesions and pustules consistent with PF. Lesions were similar to those observed in domestic animals and primarily affected the pinnae, face and nasal planum, distal legs, and tail tip. Histological evaluation of suspect PF skin lesions in affected animals, evaluation of medical records for treatments received, causative agents in the diet and environment, and special stains for infectious organisms yielded no consistent inciting cause. The Arabian oryx is a species highly adapted to arid environments of the desert and has recently survived from a severe genetic bottleneck; both of these factors may have contributed to the development of PF in these animals.

Clinical presentation, treatment and outcome in dogs with pemphigus foliaceus with and without vasculopathic lesions: an evaluation of 41 cases.

BACKGROUND: Concurrent vasculopathic lesions in dogs with pemphigus foliaceus (PF) have been observed anecdotally yet not reported in the literature. Any association with prognosis is unclear. HYPOTHESIS/OBJECTIVES: To compare clinical features and outcome of PF in dogs with and without vasculopathic lesions. ANIMALS: Archived, formalin-fixed, paraffin-embedded biopsy samples of 41 dogs with PF. METHODS AND MATERIALS: Archived, formalin-fixed, paraffin-embedded biopsy samples with a histological diagnosis of PF were selected and re-evaluated independently. Dogs were assigned to groups following histological evaluation: Group 1 (no vasculopathic lesions) and Group 2 (vasculopathic lesions present). Group 2 was subdivided into Group 2a (vasculopathic lesions without vasculitis - i.e. vasculopathy) and Group 2b (overt vasculitis). Medical records from identified cases were reviewed retrospectively for data on clinical presentation, treatment and outcome. RESULTS: Time to remission was longer in Group 2b (93.8 days) compared to Group 1 (41.8 days) (P = 0.047). Dogs in groups 2a and 2b were more likely to have systemic signs of illness at presentation (P = 0.028 and P = 0.032, respectively) compared to Group 1. Dogs in Group 2b were more likely to have adverse effects associated with treatment than dogs in Group 1 (P = 0.004). There were no significant differences in lesion type, distribution, rates of remission, recurrence or corticosteroid dosage between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with PF and concurrent vasculitis took longer to achieve remission and were more likely to have systemic signs of illness or adverse effects associated with treatment than dogs with PF without concurrent vasculopathic lesions.

Beneficial effect of oclacitinib in a case of feline pemphigus foliaceus.

Pemphigus foliaceous (PF) is a pustular, immune-mediated skin disease characterised by acantholytic cells and commonly treated with high doses of glucocorticoids. This report describes one case of feline PF successfully controlled using oral oclacitinib, suggesting a possible therapeutic alternative to glucocorticoids in some cases.

Le pemphigus foliacé (PF) est une dermatose à médiation immune pustuleuse caractérisée par des cellules acantholytiques et traitée fréquemment par des doses élevées de corticoïdes. Cet article décrit un cas de PF félin contrôlé avec succès par de l'oclacitinib orale, suggérant une alternative thérapeutique possible aux corticoïdes dans certains cas.

El pénfigo foliáceo (PF) es una enfermedad cutánea pustular, inmunomediada, caracterizada por células acantolíticas y comúnmente tratada con altas dosis de glucocorticoides. Este informe describe un caso de PF El pénfigo foliáceo (PF) es una enfermedad cutánea pustulosa, inmunomediada, caracterizada por células acantolíticas y comúnmente tratada con altas dosis de glucocorticoides. Este informe describe un caso de FP felino controlado con éxito con oclacitinib oral, lo que sugiere una posible alternativa terapéutica a los glucocorticoides en algunos casos. felino controlado con éxito con oclacitinib oral, lo que sugiere una posible alternativa terapéutica a los glucocorticoides en algunos casos.

O pênfigo foliáceo (PF) é uma dermatopatia pustular, imunomediada caracterizada por células acantolíticas e comumente tratado com altas doses de glicocorticoides. Este relato descreve um caso de PF felino satisfatoriamente controlado utilizando oclacitinib por via oral, sugerindo uma possível alternativa terapêutica aos glicocorticoides em alguns casos.

Combination therapy with azathioprine, cyclosporine and ketoconazole in a dog with concurrent pemphigus foliaceus and hyperadrenocorticism - Case report.

A 10-year-old, spayed female Shih Tzu dog presented with a history of progressive erythema and multiple crusts developing 85 days previously. The dog had been diagnosed with hyperadrenocorticism (HAC) 55 days prior to presentation and was treated with oral trilostane (2.86 mg/kg, once daily) that was discontinued due to a poor response. In addition to generalised alopecia, erythematous plaques and crusts were noted on the trunk, head and footpads. Lesional impression smears revealed numerous acantholytic cells and non-degenerated neutrophils. Histopathological findings demonstrated subcorneal pustules with acantholytic cells and intact neutrophils. On the basis of these findings, we diagnosed pemphigus foliaceus (PF) with concurrent HAC. We wished to avoid glucocorticoids and, therefore, prescribed oral, once-daily azathioprine (2 mg/kg), modified cyclosporine (7 mg/kg) and ketoconazole (5 mg/kg). By day 71 post-treatment, the erythematous crusts had almost disappeared and the alopecia had improved considerably. However, by the subsequent follow-up examination on day 99, the clinical signs had reappeared due to the tapering of cyclosporine. To the best of our knowledge, this is the first case report describing concurrent PF and HAC in a dog. Combination therapy with azathioprine, modified cyclosporine and ketoconazole was effective, and should be considered for dogs diagnosed with concurrent autoimmune diseases and HAC.

Deep pemphigus (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) in dogs, cats and horses: a comprehensive review.

Pemphigus is the term used to describe a group of rare mucocutaneous autoimmune bullous diseases characterized by flaccid blisters and erosions of the mucous membranes and/or skin. When the autoantibodies target desmosomes in the deep layers of the epidermis, deep pemphigus variants such as pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus develop. In this article, we will review the signalment, clinical signs, histopathology and treatment outcome of pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. Canine, feline and equine pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus have many features similar to the human counterpart. These chronic and often relapsing autoimmune dermatoses require aggressive immunosuppressive therapy. In animals, the partial-to-complete remission of pemphigus vulgaris and pemphigus vegetans has been achieved with high dose glucocorticoid therapy, with or without adjunct immunosuppressants; the prognosis is grave for paraneoplastic pemphigus.

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.